The Dunedin Study - DMHDRU


All peer reviewed publications are listed below.

Displaying page 1 of 23.

Oral Health-Related Quality of Life from Young Adulthood to Mid-Life | 2023
Hong, Chuen Lin; Thomson, W. Murray; Broadbent, Jonathan M.
Healthcare, 2023, 11(4), .
download pdf Our ref: RO793
Show abstract » Quality of life varies with time, often worsening, and is affected by circumstances, events, and exposures at different stages of life. Little is known about how oral health-related quality of life (OHRQoL) changes during middle age. We investigated OHRQoL changes from age 32 to 45 years among participants in a population-based birth cohort, along with clinical and socio-behavioural associations. Generalised estimating equation models were used to investigate the association between OHRQoL (assessed at ages 32, 38, and 45 years; n = 844), and the socioeconomic position in childhood (up to age 15 years) and adulthood (ages 26 through to 45 years), dental self-care (dental services utilisation and tooth brushing), oral conditions (such as tooth loss), and experiencing a dry mouth. The multivariable analyses were controlled for sex and personality traits. At each stage of life, those of a lower socioeconomic status were at greater risk of experiencing OHRQoL impacts. Those who engaged in favourable dental self-care habits (the regular use of dental services and at least twice daily tooth brushing) experienced fewer impacts. A social disadvantage at any stage of life has enduring deleterious effects on one’s quality of life in middle age. Ensuring access to timely and appropriate dental health services in adulthood may reduce the impacts of oral conditions on one’s quality of life.
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Kidney-Function Trajectories From Young Adulthood to Midlife: Identifying Risk Strata and Opportunities for Intervention | 2023
Guiney, H., Walker, R., Broadbent, ... Show all » J., Caspi, A., Goodin, E., Kokaua, J., Moffitt, T. E., Robertson, S., Theodore, R., Poulton, R., Endre, Z. « Hide
Kidney Int Rep, 2023, 8(1), 51-63.
download pdf Our ref: RO791
Show abstract » INTRODUCTION: Understanding normative patterns of change in kidney function over the life course may allow targeting of early interventions to slow or prevent the onset of kidney disease, but knowledge about kidney functional change before middle age is limited. This study used prospective longitudinal data from a representative birth cohort to examine common patterns of change from young to midadulthood and to identify risk factors and outcomes associated with poorer trajectories. METHODS: We used group-based trajectory modeling in the Dunedin study birth cohort (n = 857) to identify the following: (i) common kidney function trajectories between the ages 32 and 45 years, (ii) early-life factors associated with those trajectories, (iii) modifiable physical and psychosocial factors across adulthood associated with differences in trajectory slope, and (iv) links between trajectories and kidney-related outcomes at age 45 years. RESULTS: Three trajectory groups were identified and could be differentiated by age 32 years as follows: normal (58% of participants), low-normal (36%), and high-risk (6%) groups. Those from low socioeconomic backgrounds had higher odds of following a high-risk (vs. normal) trajectory. Modifiable factors (blood pressure, body mass index, inflammation, glycated hemoglobin, smoking, and socioeconomic status) across adulthood were associated with steeper age-related declines in kidney function, particularly among those in the low-normal and high-risk groups. Those in the low-normal and high-risk groups also had more adverse kidney-related outcomes at age 45 years. CONCLUSION: The current findings could be used to inform the development of early interventions and point to socioeconomic conditions across the life course and health-related risk factors and behaviors in adulthood as kidney health promotion targets.
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Disordered gambling in a longitudinal birth cohort: From childhood precursors to adult life outcomes | 2022
Slutske, W.S., Richmond-Rakerd, L.S., Piasecki, ... Show all » T.M., Ramrahka, S., Poulton, R., Moffitt, T.E., Caspi, A « Hide
Psychological Medicine, 2022, . 10.1017/S0033291722003051
download pdf Our ref: RO794
Show abstract » Background. Despite its introduction into the diagnostic nomenclature over four decades ago, there remain large knowledge gaps about disordered gambling. The primary aims of the present study were to document the long-term course, childhood precursors, and adult life outcomes associated with disordered gambling. Methods. Participants enrolled in the population-representative Dunedin Study were prospectively followed from birth through age 45. Disordered gambling was assessed six times from age 18; composite measures of childhood social class, general intelligence, and low self-control were based on assessments obtained from birth through age 15; adult socioeconomic, financial, and legal outcomes were obtained through age 45. Lifetime disordered gambling was predicted from the three childhood precursors and the adult outcomes were predicted from lifetime disordered gambling. Results. Past-year disordered gambling usually occurred at only a single time point and recurrence was relatively uncommon. Lower childhood social class, general intelligence, and self-control significantly predicted lifetime disordered gambling in adulthood. In turn, lifetime disordered gambling in adulthood significantly predicted occupational, educational, and financial problems in adulthood (ds =0.23–0.41). These associations were markedly reduced and sometimes rendered nonsignificant after adjusting for childhood precursors (ds =0.04–0.32). Conclusions. Socioeconomic, financial, and legal outcomes in adulthood are not merely consequences of disordered gambling, but also are predicted from childhood precursors. Deflecting the trajectories of young people at risk for developing disordered gambling may help to ameliorate not just the development of later disordered gambling, but also other associated adverse outcomes.
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Life-Course Persistent Antisocial Behavior and Accelerated Biological Aging in a Longitudinal Birth Cohort | 2022
Langevin, S., Caspi, A., Barnes, ... Show all » J. C., Brennan, G., Poulton, R., Purdy, S. C., Ramrakha, S., Tanksley, P. T., Thorne, P. R., Wilson, G., Moffitt, T. E. « Hide
Int J Environ Res Public Health, 2022, 19(21), .
download pdf Our ref: RO792
Show abstract » Prior research shows that individuals who have exhibited antisocial behavior are in poorer health than their same-aged peers. A major driver of poor health is aging itself, yet research has not investigated relationships between offending trajectories and biological aging. We tested the hypothesis that individuals following a life-course persistent (LCP) antisocial trajectory show accelerated aging in midlife. Trajectories of antisocial behavior from age 7 to 26 years were studied in the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort (N = 1037). Signs of aging were assessed at age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. First, we tested whether the association between antisocial behavior trajectories and midlife signs of faster aging represented a decline from initial childhood health. We then tested whether decline was attributable to tobacco smoking, antipsychotic medication use, debilitating illnesses in adulthood, adverse exposures in childhood (maltreatment, socioeconomic disadvantage) and adulthood (incarceration), and to childhood self-control difficulties. Study members with a history of antisocial behavior had a significantly faster pace of biological aging by midlife, and this was most evident among individuals following the LCP trajectory (beta, 0.22, 95%CI, 0.14, 0.28, p
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Improving risk indexes for Alzheimer’s disease and related dementias for use in midlife | 2022
Aaron Reuben, Terrie E. Moffitt, Wickcliffe C. Abraham, Antony Ambler, Maxwell L. Elliott, ... Show all » Ahmad R. Hariri, Honalee Harrington, Sean Hogan, Renate M. Houts, David Ireland, Annchen R. Knodt, Joan Leung, Amber Pearson, Richie Poulton, Suzanne C. Purdy, Sandhya Ramrakha, Line J.H. Rasmussen, Karen Sugden, Peter R. Thorne, Benjamin Williams, Graham Wilson, Avshalom Caspi. « Hide
Brain Communications, 2022, 4(5), .
download pdf Our ref: RO790
Show abstract » Knowledge of a person’s risk for Alzheimer’s disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife (N = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age (β's from 0.16 to 0.22), white matter hyperintensities volume (β's from 0.16 to 0.19), hippocampal volume (β's from −0.08 to −0.11), tested cognitive deficits (β's from −0.36 to −0.49), everyday cognitive problems (β's from 0.14 to 0.38), and longitudinal cognitive decline (β's from −0.18 to −0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease.
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Preparedness for healthy ageing and polysubstance use in long-term cannabis users: a population-representative longitudinal study | 2022
Meier, M.H., Caspi, A., Ambler, ... Show all » A., Hariri, A.R., Harrington, HL., Hogan, S., Houts, R., Knodt, A.R., Ramrakha, S., Richmond-Rakerd, L.S., Poulton, R., Moffitt, T. E. « Hide
The Lancet Healthy Longevity, 2022, 3(10), e703-e714.
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Our ref: RO789
Show abstract » Background Cannabis is often characterised as a young person’s drug. However, people who began consuming cannabis in the 1970s and 1980s are no longer young and some have consumed it for many years. This study tested the preregistered hypothesis that long-term cannabis users show accelerated biological ageing in midlife and poorer health preparedness, financial preparedness, and social preparedness for old age.
Methods In this longitudinal study, participants comprised a population-representative cohort of 1037 individuals born in Dunedin, New Zealand, between April, 1972, and March, 1973, and followed to age 45 years. Cannabis, tobacco, and alcohol use and dependence were assessed at ages 18 years, 21 years, 26 years, 32 years, 38 years, and 45 years. Biological ageing and health, financial, and social preparedness for old age were assessed at age 45 years. Long-term cannabis users were compared using independent samples t tests with five groups: lifelong cannabis nonusers, long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters. In addition, regression analyses tested dose–response associations for continuously measured persistence of cannabis dependence from age 18 years to 45 years, with associations adjusted for sex, childhood socioeconomic status, childhood IQ, low childhood self-control, family substance dependence history, and persistence of alcohol, tobacco, and other illicit drug dependence.
Findings Of 997 cohort members still alive at age 45 years, 938 (94%) were assessed at age 45 years. Long-term cannabis users showed statistically significant accelerated biological ageing and were less equipped to manage a range of later-life health, financial, and social demands than non-users. Standardised mean differences between longterm cannabis users and non-users were large: 0·70 (95% CI 0·46 to 0·94; p<0·0001) for biological ageing, –0·72 (–0·96 to –0·49, p<0·0001) for health preparedness, –1·08 (–1·31 to –0·85; p<0·0001) for financial preparedness, and –0·59 (–0·84 to –0·34, p<0·0001) for social preparedness. Long-term cannabis users did not fare better than long-term tobacco or alcohol users. Tests of dose–response associations suggested that cannabis associations could not be explained by the socioeconomic origins, childhood IQ, childhood self-control, and family substance-dependence history of long-term cannabis users. Statistical adjustment for long-term tobacco, alcohol, and other illicit drug dependence suggested that long-term cannabis users’ tendency toward polysubstance dependence accounted for their accelerated biological ageing and poor financial and health preparedness, although not for their poor social preparedness (β –0·10, 95% CI –0·18 to –0·02; p=0·017).
Interpretation Long-term cannabis users are underprepared for the demands of old age. Although long-term cannabis use appears detrimental, the greatest challenge to healthy ageing is not use of any specific substance, but rather the long-term polysubstance use that characterises many long-term cannabis users. Substance-use interventions should include practical strategies for improving health and building financial and social capital for healthy longevity.

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The Longitudinal Association of Childhood and Adolescent Television Viewing with Substance Use Disorders and Disordered Gambling in Adulthood up to Age 45 | 2022
McAnally, H. M. Wiki Te Oi, A. Nada-Raja, S. Hancox, R. J.
International Journal of Mental Health and Addiction, 2022, .
download pdf Our ref: RO788
Show abstract » Excessive leisure-time television viewing in childhood has been associated with a range of poorer outcomes in adulthood and may represent an early form of addictive disorder. As addictive disorders are often correlated, we tested the hypothesis that television viewing in childhood and adolescence would be longitudinally associated with adulthood substance-related and behavioural addictive disorders in a population-based cohort born in 1972/1973. Weekday television viewing time was reported at multiple ages from 5 to 15 years, and criteria for alcohol, cannabis, and tobacco use disorders and disordered gambling were assessed at multiple adult ages up to 45 years. Higher television viewing times were associated with a greater likelihood of meeting diagnostic criteria for all substance-related disorders and disordered gambling in models that were adjusted for sex (p values < 0.05). After adjustment for childhood socioeconomic status and childhood selfcontrol, mean television viewing time (hours/day) remained associated with tobacco use disorder (OR = 1.22, 95% CI = 1.04–1.42, p = 0.017) and disordered gambling (OR = 1.33, 95% CI = 1.07–1.66, p = 0.010). Excessive, leisure-time television viewing in childhood and adolescence may be a modifiable risk factor for tobacco use disorder and/or disordered gambling in later life.
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Childhood Adversity and Midlife Health: Shining a Light on the Black Box of Psychosocial Mechanisms | 2022
Bourassa, K. J., Moffitt, T. E., Harrington, ... Show all » H., Houts, R., Poulton, R., Ramrakha, S., Rasmussen, L. J. H., Wertz, J., Caspi, A. « Hide
Prevention Science, 2022, .
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Our ref: RO787
Show abstract » Adverse childhood experiences (ACEs) are associated with poorer health, which has spurred public health efforts to reduce the number of adverse events children experience. Unfortunately, it is unlikely that all ACEs can be prevented. For adults who already experienced ACEs in childhood, what psychological, social, and behavioral intervention targets might reduce risk for negative health outcomes? To provide insight into the "black box" of psychosocial mechanisms linking ACEs to poor health, our study used data from the Dunedin Study, a longitudinal cohort assessed from birth to age 45. Mediation models (N = 859) were used to examine whether candidate psychosocial variables in adulthood explained the association between childhood ACEs and health in midlife. Potential psychosocial mediators included stressful life events, perceived stress, negative emotionality, and health behaviors. Children who experienced more ACEs had poorer health in midlife. They also had significantly more stressful life events, more perceived stress, more negative emotionality, and unhealthier behaviors as adults. These mediators were each independently associated with poorer health in midlife and statistically mediated the association between ACEs and midlife health. Health behaviors evidenced the strongest indirect effect from ACEs to midlife health. Together, these psychosocial mediators accounted for the association between ACEs in childhood and health three decades later. Public health efforts to mitigate the health consequences of ACEs could aim to reduce the stressful life events people experience, reduce negative emotionality, reduce perceived stress, or improve health behaviors among adults who experienced childhood adversity.
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Is childhood oral health the ‘canary in the coal mine’ for poor adult general health. Findings from two New Zealand birth cohort studies | 2022
Ruiz, B., Broadbent, J.M., Thomson, ... Show all » W.M., Ramrakha, S., Boden, J., Horwood, L.J. Poulton, R. « Hide
Community Dentistry and Oral Epidemiology, 2022, .
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Our ref: RO786
Show abstract » Objectives: This study aimed to investigate whether childhood dental caries was associated with self-reported general health in midlife.

Methods: We used data on childhood oral health (caries experience) and adult self-reported general health from two New Zealand longitudinal birth cohorts, the Dunedin Multidisciplinary Health and Development Study (n = 922 and n = 931 at ages 5 and 45 years, respectively), and the Christchurch Health and Development Study (n = 1048 and n = 904 at ages 5 and 40 years, respectively). We used generalized estimating equations to examine associations between age-5 dental caries and self-rated general health and the number of self-reported physical health conditions at ages 45/40 (diagnosed by a doctor or health professional, n = 14 conditions among both cohorts). Covariates included known risk factors for poor health (SES, IQ, perinatal complications), and personality style, which is known to affect subjective health ratings.

Results: Incidence rate ratios for 'Excellent' self-rated health were lower among those who had high experience of dental caries as children than those who had not in both, the Dunedin (IRR, 0.76; 95% CI, 0.50, 1.14) and Christchurch studies (IRR, 0.69; 95% CI, 0.47, 1.00). Childhood dental caries was not associated with the number of self-reported physical health conditions in midlife, in either cohort. Dunedin Study members who at age 5 were not caries-free or whose parents rated their own or their child's oral health as poor were less likely to report 'Excellent' self-rated general health at age 45 than those who were caries-free and whose parents did not give a 'poor' rating (IRR, 0.69; 95% CI, 0.49, 0.97).

Conclusions: Five-year-olds with greater caries experience were more likely to have poorer self-rated general health by midlife. Beyond this longitudinal association, future research should examine whether childhood dental caries is associated with objective/biological markers of physical health and whether it may have utility as an early indicator for poor general health in adulthood.

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Parental history of positive development and child behavior in next generation offspring: A two-cohort prospective intergenerational study | 2022
Letcher, P., Greenwood, C. J., McAnally, ... Show all » H., Belsky, J., Macdonald, J. A., Spry, E. A., Thomson, K. C., O'Connor, M., Sligo, J., Youssef, G., McIntosh, J. E., Iosua, E., Hutchinson, D., Cleary, J., Sanson, A., V. Patton, G. C., Hancox, R. J., Olsson, C. A. « Hide
Child Development, 2022, 1-14.
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Our ref: RO785
Show abstract » This study examined whether positive development (PD) in adolescence and young adulthood predicts offspring behavior in two Australasian intergenerational cohorts. The Australian Temperament Project Generation 3 Study assessed PD at age 19-28 (years 2002-2010) and behavior in 1165 infants (12-18 months; 608 girls) of 694 Australian-born parents (age 29-35; 2012-2019; 399 mothers). The Dunedin Multidisciplinary Health and Development Parenting Study assessed PD at age 15-18 (years 1987-1991) and behavior in 695 preschoolers (3-5 years; 349 girls) and their New Zealand born parents (age 21-46; 1994-2018; 363 mothers; 89% European ethnicity). In both cohorts, PD before parenthood predicted more positive offspring behavior (betarange = .11-.16) and fewer behavior problems (betarange = -.09 to -.11). Promoting strengths may secure a healthy start to life.
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Diminished structural brain integrity in long-term cannabis users reflects a history of polysubstance use | 2022
Knodt, A.R., Meier, M.H., Ambler, ... Show all » A., Gehred, M.Z., Harrington, H., Ireland, D., Poulton, R., Ramrakha, S., Caspi, A., Moffitt, T.E., Hariri, A.R. « Hide
Biological Psychiatry, 2022, .
download pdf Our ref: RO784
Show abstract » Background
Cannabis legalization and use are outpacing our understanding of its long-term effects on brain and behavior, which is fundamental for effective policy and health practices. Existing studies are limited by small samples, cross-sectional measures, failure to separate long-term from recreational use, and inadequate control for other substance use. Here, we address these limitations by determining the structural brain integrity of long-term cannabis users in the Dunedin Study, a longitudinal investigation of a population-representative birth cohort followed to midlife.
We leveraged prospective measures of cannabis, alcohol, tobacco, and other illicit drug use, in addition to structural neuroimaging in 875 Study members at age 45 to test for differences in both global and regional grey and white matter integrity between long-term cannabis users and lifelong non-users. We additionally tested for dose-response associations between continuous measures of cannabis use and brain structure, including careful adjustments for use of other substances.
Long-term cannabis users had a thinner cortex, smaller subcortical grey matter volumes, and higher machine-learning-predicted brain age than non-users. However, these differences in structural brain integrity were explained by the propensity of long-term cannabis users to engage in polysubstance use, especially with alcohol and tobacco.
These findings suggest that diminished midlife structural brain integrity in long-term cannabis users reflects a broader pattern of polysubstance use, underlining the importance of understanding comorbid substance use in efforts to curb the negative effects of cannabis on brain and behavior as well as establish more effective policy and health practices.

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Is repeated childhood fracture related to areal bone density or body composition in middle age? | 2022
Meredith‑Jones K., Haszard J., Taylor R., Waters D., Hogan S., ... Show all » Ramrakha S., Poulton R. « Hide
Osteoporos International, 2022, .
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Our ref: RO782
Show abstract » Childhood fracture is common, but whether it predicts adult fracture is not clear. Repeat childhood fracture was associated with adult ( INTRODUCTION: A quarter of boys and 15% of girls will suffer multiple fractures, but it is not clear whether multiple fractures during growth predict fracture risk and areal bone density in adulthood. This study evaluated whether children who repeatedly fracture were at increased risk of low areal bone density, abnormal body composition, and fractures by age 45. METHODS: A subsample of a large birth cohort study with childhood fracture cases had areal bone density assessed at age 45 years. Participants were questioned regularly across their lifetime about fractures during childhood (ages 0-18 years of age) and adulthood (any fracture between 18 and 45 years). The number of fractures was collapsed into three categories: no fractures; 1 fracture; and > 1 fracture, separately for child and adult groups.
RESULTS: At age 45 years, areal bone mineral density (g/cm(2)) and body composition were measured with dual X-ray absorptiometry in n = 555 participants. Compared to no fractures, twice as many girls (14% vs 7%, P = 0.156) and boys (31.4% vs 14.1%, P = 0.004) who repeatedly fractured in childhood sustained multiple fractures as adults. Both girls and boys who were fracture-free tended to remain fracture-free as adults (79.8% compared with 62.8%, P = 0.045, and 64.8% compared with 51.4%, P = 0.025, in males and females, respectively). Participants were more than twice as likely to fracture repeatedly as adults if they had sustained multiple fractures as a child (OR 2.5 95% CI: 1.4, 4.6). Women who repeatedly fractured during childhood had lower areal bone density, whereas repeated fracturing during childhood was not associated with areal bone density or body composition in men, even after adjustment for other factors known to influence fracture history.
CONCLUSION: Childhood fracture history is associated with persistent skeletal fragility in adulthood (
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The prevalence of glaucoma in 45-year-old New Zealanders | 2022
Singh, A., Gale, J., Cheyne, ... Show all » K., Ambler, A., Poulton, R., Wilson, G. « Hide
New Zealand Medical Journal , 2022, 135 .
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Our ref: NZ102
Show abstract » aim: We aimed to estimate the prevalence of glaucoma in New Zealand using a population-based birth cohort of 45-year-olds.
methods: Study members of the Dunedin Multidisciplinary Health & Development Study participated (n=938 out of 1037 births (91%)). The data collected included visual acuity, visual field (VF), refraction, central corneal thickness, intraocular pressure (IOP), axial length, spectral domain optical coherence tomography (OCT), and non-mydriatic fundus photographs. Two phthalmologists reviewed data independently to generate a consensus glaucoma status: “Normal” if no suspicion of glaucoma; “Ocular hypertension” if IOP >21 mmHg; “Glaucoma suspect” if optic disc photograph was suspicious for glaucoma with no more than borderline or non-corresponding VF or OCT abnormalities; and “Glaucoma” if optic disc photograph was suspicious for glaucoma and there were corresponding abnormalities of the OCT or VF.
results: Of 891 participants with sufficient data to assign a glaucoma status, 804 were “Normal” (90.2% [CI 88.3–92.2]), 15 were “Ocular hypertension” (1.68% [95% confidence interval (CI) .84–2.5]), 65 were “Glaucoma suspect” (7.30% [95% CI 5.6–9.0]), and 7 were classified as “Glaucoma” (0.79% [95% CI 0.21–1.4]). An additional 73 participants (8.2%, [95% CI 6.3%–10%]) had abnormalities on the OCT scan but were not deemed to be glaucoma suspects.
conclusion: The prevalence of glaucoma in New Zealand is between 0.2% and 1.4%, consistent with other population-based studies in the same age group. The study highlights the sensitivity of OCT and the potential for misinterpretation and over-investigation.

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Using a loneliness measure to screen for risk of mental health problems: A replication in two nationally-representative cohorts | 2022
Matthews, T., Bryan, B. T., Danese, ... Show all » A., Meehan, A., Poulton, R., & Arseneault, L. « Hide
International Journal of Environmental Research and Public Health, 2022, .
download pdf Our ref: RO779
Show abstract » Background: Loneliness co-occurs alongside many mental health problems and is associated with poorer treatment outcomes. It could therefore be a phenomenon of interest to clinicians, as an indicator of generalised risk for psychopathology. The present study tested whether a short measure of loneliness can accurately classify individuals who are at increased risk of common mental health problems. Methods: Data were drawn from two nationally-representative cohorts: the age-18 wave of the UK-based Environmental Risk (E-Risk) Longitudinal Twin Study, and the age-38 wave of the New Zealand-based Dunedin Multidisciplinary Health and Development Study. In both cohorts, loneliness was assessed using the 3-item UCLA Loneliness Scale, plus two stand-alone items about feeling alone and feeling lonely. Outcome measures consisted of diag-noses of depression and anxiety, and self-reports of self-harm/suicide attempts, assessed via structured interview. Results: ROC curve analysis showed that the loneliness scale had fair accu-racy in classifying individuals meeting criteria for all three outcomes, with a cut-off score of 5 (on a scale from 3 to 9) having the strongest empirical support. Both of the stand-alone items showed modest sensitivity and specificity, but were more limited in their flexibility. The find-ings replicated across the two cohorts, indicating that they are applicable both to younger and older adults. In addition, the accuracy of the loneliness scale in detecting mental health problems was comparable to a measure of poor sleep quality, a phenomena which is often included in screening tools for depression and anxiety. Conclusions: These findings indicate that a loneliness measure could have utility in mental health screening contexts, as well as in research.
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Childhood caries experience in two Aotearoa New Zealand birth cohorts: implications for research, policy and practice | 2022
Ruiz, Begoña, Broadbent, Jonathan M., Thomson, ... Show all » W. Murray, Ramrakha, Sandhya, Boden, Joe, John Horwood, L., Poulton, Richie « Hide
Journal of the Royal Society of New Zealand, 2022, 1-18.
download pdf Our ref: NZ101
Show abstract » Oral health in Aotearoa New Zealand has improved in the last seven decades, but improvements among young children have stagnated in the last two. Four out of ten 5-year-olds are affected by caries and many pre-schoolers require dental treatment under general anaesthesia. We analysed data from two longitudinal studies, the Dunedin Multidisciplinary Health and Development Study and the Christchurch Health and Development Study. We compared their methods, cohort characteristics and childhood oral health findings and discuss their implications for policy, research, and practice. Age 5 dmft was obtained in the Dunedin Study from clinical examinations, and from School Dental Service records in the Christchurch Study. Findings were consistent with respect to childhood socioeconomic status, exposure to community water fluoridation, and maternal education. Despite overall improvements, caries rates remain relatively unchanged: dmft in these cohorts, measured in the 1970s–1980s, resemble New Zealand’s statistics for 5-year-olds in the 2000s. Notwithstanding the steep caries decline observed over the years, the caries distribution has shifted, hereby the greatest severity of disease is now concentrated among a smaller group of the most deprived children. Early childhood caries appears to be a useful indicator of deprivation that should inform interventions for
those in greatest need.

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Lifetime cannabis exposure and small airway function in a population-based cohort study | 2022
Tan, Hua Shin, McAnally, Helena, M. Dummer, ... Show all » Jack, Hancox, Robert J. « Hide
ERJ Open Research, 2022, 8(2), .
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Our ref: RO778
Show abstract » Background and objective: The long-term effects of cannabis on small airway function remain unclear. We investigated associations between cannabis use and small airway function in a general population sample.
Methods: Cannabis use was ascertained at multiple ages from age 18 to 45 years and quantified as joint-years among 895 participants in the Dunedin Multidisciplinary Health and Development Study. Small airway function at ages 38 and 45 years was measured using impulse oscillometry before and after inhalation of salbutamol. Analyses used multiple linear regression adjusting for tobacco use, body mass index, and height. Longitudinal analyses of cannabis use between 38 and 45 years also adjusted for IOS at age 38.
Results: Lifetime cannabis joint-years with IOS differed between men and women: in women, cannabis use was associated with pre-bronchodilator R5, R20, X5, AX, and Fres and marginally associated with R5-R20. Cannabis use was not statistically significantly associated with any of the pre-bronchodilator IOS measures in men. Cannabis use between ages 38 and 45 was associated with a similar pattern of changes in IOS measures. After salbutamol, cannabis use was only statistically significantly associated with R5 and R20 among women and none of the IOS measures among men.
Conclusions: Cannabis use is associated with small airway dysfunction at age 45 years, indicating an increase in peripheral airway resistance and reactance. These associations were greater and only statistically significant among women. Associations were weaker and mostly non-significant after bronchodilator use suggesting that cannabis-induced changes in small airways may be at least partially reversible.

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Long-term Cannabis Users Show Lower Cognitive Reserves and Smaller Hippocampal Volume in Midlife | 2022
Madeline H. Meier, Ph.D., Avshalom Caspi, Ph.D., Annchen R. Knodt, ... Show all » M.Sc., Wayne Hall, Ph.D., Antony Ambler, M.Sc., HonaLee Harrington, B.A., Sean Hogan, B.A., Renate M. Houts, Ph.D., Richie Poulton, Ph.D., Sandhya Ramrakha, Ph.D., Ahmad R. Hariri, Ph.D., Terrie E. Moffitt, Ph.D. « Hide
American Journal of Psychiatry, 2022, 179(5), 362-374.
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Our ref: RO777
Show abstract » Objective: Cannabis use is increasing among midlife and older adults. This study tested the hypotheses that long-term cannabis use is associated with cognitive deficits and smaller hippocampal volume in midlife, which is important because midlife cognitive deficits and smaller hippocampal volume are risk factors for dementia.
Methods: Participants are members of a representative cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972–1973 and followed to age 45, with 94% retention. Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.
Results: Long-term cannabis users showed IQ decline from childhood to midlife (mean525.5 IQ points), poorer learning and processing speed relative to their childhood IQ, and informant-reported memory and attention problems. These deficits were specific to long-term cannabis users because they were either not present or were smaller among long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters.Cognitive deficits among long-termcannabis users could not be explained by persistent tobacco, alcohol, or other illicit drug use, childhood socioeconomic status, low childhood self-control, or family history of substance dependence. Long-term cannabis users showed smaller hippocampal volume, but smaller hippocampal volume did not statistically mediate cannabis-related cognitive deficits.
Conclusions: Long-term cannabis users showed cognitive deficits and smaller hippocampal volume in midlife. Research is needed to ascertain whether long-term cannabis users show elevated rates of dementia in later life.

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DunedinPACE: a DNA methylation biomarker of the Pace of Aging | 2022
Belsky, D.W., Caspi, A., Corcoran, ... Show all » D.L., Sugden, K., Poulton, R., Arseneault, L., Baccarelli, A., Chamarti, K., Gao, X., Hannon, E., Harrington, H.L., Houts, R., Kothari, M., Kwon, D., Mill, J., Schwartz, J., Vokonas, P., Wang, C., Williams, B., and Moffitt, T.E. « Hide
eLife, 2022, .
download pdf Our ref: RO776
Show abstract » Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).
Methods: We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named Dunedin-PACE, in five additional datasets.
Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.
Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.

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Deep-seated psychological histories of COVID-19 vaccine hesitance and resistance | 2022
Terrie E. Moffitt, Avshalom Caspi, Antony Ambler, Kyle Bourassa , HonaLee Harrington, ... Show all » Sean Hogan, Renate Houts, Sandhya Ramrakha, Stacy L. Wood, Richie Poulton. « Hide
PNAS Nexus, 2022, .
download pdf Our ref: RO775
Show abstract » To design effective pro-vaccination messaging, it is important to know ―where people are coming from‖—the personal experiences and long-standing values, motives, lifestyles, preferences, emotional tendencies, and information-processing capacities of people who end up resistant or hesitant toward vaccination. We used prospective data from a 5-decade cohort study spanning childhood to midlife to construct comprehensive early-life psychological histories of groups who differed in their vaccine intentions in months just before COVID vaccines became available in their country. Vaccine-resistant and vaccine-hesitant participants had histories of adverse childhood experiences that foster mistrust, longstanding mental-health problems that foster misinterpretation of messaging, and early-emerging personality traits including tendencies toward extreme negative emotions, shutting down mentally under stress, nonconformism, and fatalism about health. Many vaccine-resistant and -hesitant participants had cognitive difficulties in comprehending health information. Findings held after control for socioeconomic origins. Vaccine intentions are not short-term isolated misunderstandings. They are part of a person's style of interpreting information and making decisions that is laid down before secondary school age. Findings suggest ways to tailor vaccine messaging for hesitant and resistant groups. To prepare for future pandemics, education about viruses and vaccines before or during secondary schooling could reduce citizens‘ level of uncertainty during a pandemic, and provide people with pre-existing knowledge frameworks that prevent extreme emotional distress reactions and enhance receptivity to health messages. Enhanced medical technology and economic resilience are important for pandemic preparedness, but a prepared public who understands the need to mask, social distance, and vaccinate will also be important.
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Associations between retinal nerve layer and ganglion cell layer in middle age and cognition from childhood to adulthood. | 2022
Barrett-Young. A., Ambler, A., Cheyne, K., ... Show all » Guiney, H., Kokaua, J., Steptoe, B., Tham, Y.C., Wilson, G.A., Wong, T.Y., Poulton, R. « Hide
JAMA Opthalmology , 2022, .
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Our ref: RO774
Show abstract » Importance The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) have been proposed as potential biomarkers for Alzheimer disease (AD). Although a number of studies have shown that knowing the thickness of RNFL and GCL can help differentiate between patients with AD and healthy controls, it is unclear whether these associations are observable earlier in life.

Objective To examine whether RNFL and GCL thickness was associated with global cognitive performance in middle age and in childhood and with a decline in cognitive performance from childhood to adulthood and whether RNFL and GCL thickness was associated with decline in specific cognitive domains over the same period.

Design, Setting, and Participants This longitudinal cohort study involved members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal representative birth cohort from New Zealand (n = 1037). Participants were born in 1972 to 1973 and followed up until age 45 years, with 94% of the living cohort still participating.

Main Outcomes and Measures Cognitive performance (Full Scale IQ, processing speed, perceptual reasoning, and verbal comprehension) measured at ages 7, 9, and 11 years (mean value) and age 45 years, and RNFL and GCL thickness measured via optical coherence tomography (OCT) at age 45 years.

Results Data were analyzed between August 2020 and April 2021. Data from 865 participants were included in the present study (50.2% male, 49.8% female; 92.2% of the 938 study members seen at age 45 years). Of the 73 participants who were excluded, 63 were excluded because of issues with OCT scans and 10 were excluded because of diseases affecting the retina. Thinner RNFL and GCL were associated with lower Full Scale IQ in childhood and at age 45 years. Thinner RNFL was also associated with a greater decline in processing speed from childhood to adulthood.

Conclusions and Relevance RNFL and GCL thickness in middle age was associated with cognitive performance in childhood and adulthood, and thinner RNFL with a decline in processing speed between childhood and adulthood. These data emphasize the potential utility of OCT measures as biomarkers of cognitive function; however, further longitudinal studies are needed to determine whether retinal thinning precedes cognitive decline and whether other confounding factors may account for this association.

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Association of Treatable Health Conditions During Adolescence With Accelerated Aging at Midlife | 2022
Bourassa, K., Moffitt, T.E., Ambler, ... Show all » A., Hariri, A.R., Harrington, H., Houts, R., Ireland, D., Knodt, A., Poulton, R., Ramrakha, S., Caspi, A. « Hide
JAMA Pediatrics , 2022, .
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Our ref: RO773
Show abstract » Importance Biological aging is a distinct construct from health; however, people who age quickly are more likely to experience poor health. Identifying pediatric health conditions associated with accelerated aging could help develop treatment approaches to slow midlife aging and prevent poor health in later life.

Objective To examine the association between 4 treatable health conditions in adolescence and accelerated aging at midlife.

Design, Setting, and Participants This cohort study analyzed data from participants in the Dunedin Study, a longitudinal investigation of health and behavior among a birth cohort born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, and followed up until age 45 years. Participants underwent an assessment at age 45 years and had data for at least 1 adolescent health condition (asthma, smoking, obesity, and psychological disorders) and outcome measure (pace of aging, gait speed, brain age, and facial age). Data analysis was performed from February 11 to September 27, 2021.

Exposures Asthma, cigarette smoking, obesity, and psychological disorders were assessed at age 11, 13, and 15 years.

Main Outcomes and Measures The outcome was a midlife aging factor composite score comprising 4 measures of biological aging: pace of aging, gait speed, brain age (specifically, BrainAGE score), and facial age.

Results A total of 910 participants (459 men [50.4%]) met the inclusion criteria, including an assessment at age 45 years. Participants who had smoked daily (0.61 [95% CI, 0.43-0.79] SD units), had obesity (0.82 [95% CI, 0.59-1.06] SD units), or had a psychological disorder diagnosis (0.43 [95% CI, 0.29-0.56] SD units) during adolescence were biologically older at midlife compared with participants without these conditions. Participants with asthma were not biologically older at midlife (0.02 [95% CI, −0.14 to 0.19] SD units) compared with those without asthma. These results remained unchanged after adjusting for childhood risk factors such as poor health, socioeconomic disadvantage, and adverse experiences.

Conclusions and Relevance This study found that adolescent smoking, obesity, and psychological disorder diagnoses were associated with older biological age at midlife. These health conditions could be treated during adolescence to reduce the risk of accelerated biological aging later in life.

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Differential Effects of Cannabis and Tobacco on Lung Function in Mid-Adult Life | 2022
Robert J Hancox, Andrew R Gray, Xian Zhang, Richie Poulton, Terrie E. Moffitt, ... Show all » Avshalom Caspi, Malcolm R Sears « Hide
American Journal of Respiratory and Critical Care Medicine, 2022, .
download pdf Our ref: RO772
Show abstract » Rationale. Evidence suggests that the effects of smoking cannabis on lung function are different to tobacco. However, long-term follow-up data are scarce, and mostly based on young adults. Objective. To assess the effects of cannabis and tobacco on lung function in mid-adult life. Methods. Cannabis and tobacco use were reported at ages 18, 21, 26, 32, 38, and 45 years in a population-based cohort study of 1037 participants. Spirometry, plethysmography, and carbon monoxide transfer factor were measured at age 45. Associations between lung function and cannabis use were adjusted for tobacco use. Measurements and Main Results. Data were available from 881 (88%) of 997 surviving participants. Cumulative cannabis use was associated with lower Forced Expiratory Volume in one second to Forced Vital Capacity ratios, due to a tendency towards higher Forced Vital Capacities. Cannabis use was also associated with higher total lung capacity, functional residual capacity, residual volume, and alveolar volume along with lower mid-expiratory flows, airway conductance, and transfer factor. Quitting regular cannabis use between assessments was not associated with changes in spirometry. Conclusions. Cannabis use is associated with higher lung volumes suggesting hyperinflation. There is evidence of increased large-airways resistance and lower mid-expiratory airflow, but impairment of Forced Expiratory Volume in one second to Forced Vital Capacity ratio is due to higher Vital Capacities. This pattern of effects is different to those of tobacco. We provide the first evidence that lifetime cannabis use may be associated with impairment of gas transfer.
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Changes in incisor relationship over the life course - Findings from a cohort study | 2022
Olliver SJ., Broadbent JM., Prasad, S., Cai, ... Show all » C., Thomson, W. M., Farella, M., « Hide
Journal of Dentistry, 2022, 117 .
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Our ref: RO771
Show abstract » OBJECTIVE: The aim of this longitudinal cohort study was to investigate the changes in incisor relationship over three decades from adolescence to mid-adulthood. MATERIALS AND METHODS: The sample included 1,037 children (48.4% female) born between April 1972 and March 1973 from the longitudinal birth cohort Dunedin Multidisciplinary Health and Development Study. Overjet and overbite values were assessed at age 15 and 45 years and entered in a regression model as outcome variables. Baseline occlusal variables, sex, history of orthodontic treatment, periodontal data recorded at age 38, and self-reported oral parafunction and orthodontic treatment history recorded at age 45 were entered as covariates in the regression analysis. RESULTS: Regression modelling showed that overjet/overbite category (high or low) at age 15 tends to predict overjet/overbite category at age 45, with overjet become slightly larger (around +0.5mm) and overbite slightly lower (-0.5mm) over time. Study members with self-reported tooth clenching had a slighter greater overbite (+0.3mm) at age 45 than those who did not. Additionally, those with signs of periodontal disease at age 38 had a slightly larger overjet (+0.5mm) at age 45 than those without disease. Sex differences were demonstrated with females having 0.6 mm larger overjet, and 0.4 mm overbite at age 45. CONCLUSIONS: Overall, overjet values tend to be higher during mid-adulthood than during adolescence, while the converse is true for overbite. There appears to be a degree of sexual dimorphism in overjet and overbite values later in life. CLINICAL SIGNIFICANCE: Incisor relationships change during the life course and are related to ageing, sex, periodontal health, and parafunctional habits. Clinicians and educators should be aware of these changes when making treatment decisions that alter incisor relationship.
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The Dunedin study after half a century: reflections on the past, and course for the future | 2022
Poulton, Richie. Guiney, Hayley. Ramrakha, Sandhya. Moffitt, Terrie E.
Journal of the Royal Society of New Zealand, 2022, 1-20.
download pdf Our ref: NZ98
Show abstract » Over the last 50 years Dunedin Study researchers have published more than 1400 peer-reviewed journal articles, books, and reports on many aspects of human health and development. In this 50th anniversary piece we reflect on (i) our historical roots and necessary re-invention through time; (ii) the underpinning principles that have contributed to our success; (iii) some selected examples of high-impact work from the behavioural, oral health, and respiratory domains; (iv) some of the challenges we have encountered over time and how to overcome these; and (vi) review where we see the Study going in the future. We aim to present some of the ‘back story’, which is typically undocumented and oft lost to memory, and thus focus on ‘know-how’. Our hope is to humanise our research, share insights, and to acknowledge the real heroes of the Study – the 1037 Study members, their families and their friends, who have collectively given so much, for so long, in the hope of helping others.
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Genomic and phenomic insights from an atlas of genetic effects on DNA methylation. | 2021
Min J.L., Hemani, G., Hannon, E., ... Show all » Dekkers, K.F., Castillo-Fernandez, J., Luijk, R., Carnero-Montoro, E., Lawson, D.J., Burrows, K., Suderman, M., Bretherick, A.D., Richardson, T.G., Klughammer, J., Iotchkova, V., Sharp, G., Khleifat, A.A., Shatunov, A., Iacoangeli, A., McArdie, W.L., Ho, K.M., Kumar, A., Soderhall, C., Soriano-Tarraga, C., Giralt-Steinhauer, E., Kazmi, N., Mason, D., McRae, A.F., Corcoran, D.L., Sugden, K., Kasela, S., Cardona, A., Day, F.R., Cugliari, G., Viberti, C., Guarrera S., Lerro, M., Gupta, R., Bollepalli, S., Mandaviya, P., Zeng, Y., Clarke, T-K., Walker, R.M., Schmoll, V., Czamara, D., Ruiz-Arenas, C., Rezwan, F.I., Marioni, R.E., Lin, T., Awaloff, Y., Germain, M., Aissi, D., Zwamborn, R., van Eijk, K., Dekker, A., van Dongen, J., Hottenga, J-J., Willemsen, G., Xu, C-J., Barturen, G., Catala-Moll, F., Kerick, M., Wang, C., Melton, P., Elliot, H.R., Shin, J., Bernard, M., Yet, I., Smart, M., Gorrie-Stone, T., BIOS Consortium., Shaw, C., Al Chalabi, A., Ring, S.M., Pershagen, G., Melen, E., Jimenez-Conde, J., Roquer, J., Lawlor, D., Wright, J., Martin, N.G., Montgomery, G.W., Moffitt, T.E., Poulton, R., Esko, T., Milani, L., Metspalu, A., Perry, J.R.B., Ong, K.K., Wareham, N.J., Matullo, G., Sacerdote, C., Panico, S., Caspi, A., Arseneault, L., Gagnon, F., Ollikainen, M., Kaprio, J., Felix, J.F., Rivadeneira, F., Tiemeier, H., van IJzendoorn, M.H., Uitterlinden, A.G., Jaddoe, V.W.V., Haley, C., McIntosh, A.M., Evans, K.L., Murray, A., Raikkonen, K., Lahti, J., Nohr, E.A., Sorensen T.I.A., Hansen, T., Morgen, C.S., Binder, E.B., Lucae, S., Gonzalez, J.R., BustamanteSunyer, J., Holloway, J.W., Karmaus, W., Zhang, H., Deary, I.J., Wray, N., Starr, J.M., Beekman, M., van Heemst, D., Slagboom, P.E., Morange, P-E., Tregouet, D-A., Veldink, J.H., Davies, G.E., de Geus, E.J.C., Boomsma, D.I., Vonk, J.M., Brunekreef, B., Koppelman, G.H., Alarcon-Riquelme, M.E., Huang, R-C., Pennell, C., van MeuIkram, M.A., Hughes, A.D., Tillin, T., Chaturvedi N., Pausova, Z., Paus, T., Spector, T.D., Kumari, M., Schalkwyk, L.C., Visscher, P.M., Davey-Smith, G., Bock, C., Gaunt, T.R., Bell, J.T., Heijmans, B.T., Mill, J., and Relton, C.L. « Hide
Nature Genetics , 2021, 53 1311–1321.
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Our ref: RO781
Show abstract » Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.
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A deep-learning system for the assessment of cardiovascular disease risk via the measurement of retinal vessel calibres. | 2021
Cheung, CL., Xu D., Cheng., C., ... Show all » Sabanayagam, C., Tham, Y.C., Yu, M., Rim, T., Chaoi, C.Y., Gopinath, B., Mitchell, P., Poulton, R., Moffitt, T., Caspi, A., Yam, J., Tham, C., Jonas, J., Wang, Y.X., Song, S.J., Burrell, L., Farouque, O., Li, L.J., Tan, G., Ting, D., Hsu, W., Lee, M.L., Wong, T. « Hide
Nature Biomedical Engineering, 2021, 5 498-508.
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Our ref: RO780
Show abstract » Retinal blood vessels provide information on the risk of cardiovascular disease (CVD). Here, we report the development and validation of deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs, using diverse multiethnic multicountry datasets that comprise more than 70,000 images. Retinal-vessel calibre measured by the models and by expert human graders showed high agreement, with overall intraclass correlation coefficients of between 0.82 and 0.95. The models performed comparably to or better than expert graders in associations between measurements of retinal-vessel calibre and CVD risk factors, including blood pressure, body-mass index, total cholesterol and glycated-haemoglobin levels. In retrospectively measured prospective datasets from a population-based study, baseline measurements performed by the deep-learning system were associated with incident CVD. Our findings motivate the development of clinically applicable explainable end-to-end deep-learning systems for the prediction of CVD on the basis of the features of retinal vessels in retinal photographs.
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Are macular drusen in midlife a marker of accelerated biological ageing? | 2021
Graham A Wilson, Kirsten Cheyne, Sandhya Ramrakha, Antony Ambler, Gavin SW Tan, ... Show all » Avshalom Caspi, Ben Williams, Karen Sugden, Renate Houts, Rachael L Niederer, Tien Yin Wong, Terrie E Moffitt, Richie Poulton « Hide
Clinical and Experimental Optometry, 2021, 1-6.
download pdf Our ref: RO770
Show abstract » Clinical relevance: Macular drusen are associated with age-related maculopathy but are not an ocular manifestation or biomarker of systemic ageing.
Background: Macular drusen are the first sign of age-related maculopathy, an eye disease for which age is the strongest risk factor. The aim of this cohort study was to investigate whether macular drusen in midlife – a sign of the earliest stages of age-related macular degeneration (AMD) – are
associated with accelerated biological ageing more generally.
Methods: Members of the long-running Dunedin Multidisciplinary Health and Development Study (hereafter the Dunedin Study, n = 1037) underwent retinal photography at their most recent assessment at the age of 45 years. Images were graded for the presence of AMD using a simplified
scale from the Age-Related Eye Disease Study (AREDS). Accelerated ageing was assessed by (i) a measure of Pace of Ageing defined from a combination of clinical and serum biomarkers obtained at ages 26, 32, 38, and 45 years and (ii) Facial Ageing, defined from photographs obtained at age 38 and 45 years.
Results: Of the 938 participants who participated at the age 45 assessments, 834 had gradable retinal photographs, and of these 165 (19.8%) had macular drusen. There was no significant difference in Pace of Ageing (p = .743) or Facial Ageing (p = .945) among participants with and without macular drusen.
Conclusions: In this representative general population sample, macular drusen in midlife were not associated with accelerated ageing. Future studies tracking longitudinal changes in drusen number and severity at older ages may reveal whether drusen are a biomarker of accelerated ageing.

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Does having children affect women's oral health? A longitudinal study | 2021
Morelli, E. L., Broadbent, J. M., Knight, ... Show all » E. T., Leichter, J. W., Thomson, W. M. « Hide
J Public Health Dentistry, 2021, .
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Our ref: RO769
Show abstract » BACKGROUND: Many believe women's oral health deteriorates as a result of having children. If so, such associations should exist among women but not among men. The aims of this study were to investigate whether number of children is associated with experience of dental disease and tooth loss among both men and women and to examine whether this association is affected by other variables of interest. METHODS: This study used data from the Dunedin Multidisciplinary Health and Development study, a longitudinal study of 1037 individuals (48.4% female) born from April 1972 to March 1973 in Dunedin, New Zealand, who have been examined repeatedly from birth to age 45 years. RESULTS: Data were available for 437 women and 431 men. Those with low educational attainment were more likely to have more children and began having children earlier in life. Having more children was associated with experiencing more dental caries and tooth loss by age 45, but this association was dependent on the age at which the children were had. Those entering parenthood earlier in life (by age 26) had poorer dental health than those entering parenthood later in life, or those without children. There was no association between number of children and periodontal attachment loss (PAL). Low educational attainment, poor plaque control, never routine dental attendance, and smoking (for PAL) were associated with PAL, caries experience, and tooth loss. CONCLUSIONS: Social factors associated with both the timing of reproductive patterns and health behaviors influence the risk of dental disease and its management.
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Midlife Cardiovascular Fitness Is Reflected in the Brain's White Matter | 2021
d'Arbeloff, T., Elliott, M. L., Knodt, ... Show all » A. R., Sison, M., Melzer, T. R., Ireland, D., Ramrakha, S., Poulton, R., Caspi, A., Moffitt, T. E., Hariri, A. R. « Hide
Frontiers in Aging Neuroscience, 2021, 13 .
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Our ref: RO768
Show abstract » Disappointing results from clinical trials designed to delay structural brain decline and the accompanying increase in risk for dementia in older adults have precipitated a shift in testing promising interventions from late in life toward midlife before irreversible damage has accumulated. This shift, however, requires targeting midlife biomarkers that are associated with clinical changes manifesting only in late life. Here we explored possible links between one putative biomarker, distributed integrity of brain white matter, and two intervention targets, cardiovascular fitness and healthy lifestyle behaviors, in midlife. At age 45, fractional anisotropy (FA) derived from diffusion weighted MRI was used to estimate the microstructural integrity of distributed white matter tracts in a population-representative birth cohort. Age-45 cardiovascular fitness (VO2Max; N = 801) was estimated from heart rates obtained during submaximal exercise tests; age-45 healthy lifestyle behaviors were estimated using the Nyberg Health Index (N = 854). Ten-fold cross-validated elastic net predictive modeling revealed that estimated VO2Max was modestly associated with distributed FA. In contrast, there was no significant association between Nyberg Health Index scores and FA. Our findings suggest that cardiovascular fitness levels, but not healthy lifestyle behaviors, are associated with the distributed integrity of white matter in the brain in midlife. These patterns could help inform future clinical intervention research targeting ADRDs.
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Association of subcortical gray-matter volumes with life-course-persistent antisocial behavior in a population- representative longitudinal birth cohort | 2021
Carlisi, Christina O., Moffitt, Terrie E., Knodt, ... Show all » Annchen R., Harrington, HonaLee, Langevin, Stephanie, Ireland, David, Melzer, Tracy R., Poulton, Richie, Ramrakha, Sandhya, Caspi, Avshalom, Hariri, Ahmad R., Viding, Essi « Hide
Development and Psychopathology, 2021, 1-11.
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Our ref: RO767
Show abstract » Neuropsychological evidence supports the developmental taxonomy theory of antisocial behavior, suggesting that abnormal brain development distinguishes life-course-persistent from adolescence-limited antisocial behavior. Recent neuroimaging work confirmed that prospectively- measured life-course-persistent antisocial behavior is associated with differences in cortical brain structure. Whether this extends to subcortical brain structures remains uninvestigated. This study compared subcortical gray-matter volumes between 672 members of the Dunedin Study previously defined as exhibiting life-course-persistent, adolescence-limited or low-level antisocial behavior based on repeated assessments at ages 7–26 years. Gray-matter volumes of 10 subcortical structures were compared across groups. The lifecourse- persistent group had lower volumes of amygdala, brain stem, cerebellum, hippocampus, pallidum, thalamus, and ventral diencephalon compared to the low-antisocial group. Differences between life-course-persistent and adolescence-limited individuals were comparable in effect size to differences between life-course-persistent and low-antisocial individuals, but were not statistically significant due to less statistical power. Gray-matter volumes in adolescence-limited individuals were near the norm in this population-representative cohort and similar to volumes in low-antisocial individuals. Although this study could not establish causal links between brain volume and antisocial behavior, it constitutes new biological evidence that all people with antisocial behavior are not the same, supporting a need for greater developmental and diagnostic precision in clinical, forensic, and policy-based interventions.
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Vital personality scores and healthy aging: Life-course associations and familial transmission | 2021
J. Wertz, S. Israel, L. Arseneault, D. W. Belsky, K. J. Bourassa, ... Show all » H. Harrington, et al. « Hide
Social Science & Medicine, 2021, 285 .
download pdf Our ref: RO766
Show abstract » Objectives Personality traits are linked with healthy aging, but it is not clear how these associations come to manifest across the life-course and across generations. To study this question, we tested a series of hypotheses about (a) personality-trait prediction of markers of healthy aging across the life-course, (b) developmental origins, stability and change of links between personality and healthy aging across time, and (c) intergenerational transmission of links between personality and healthy aging. For our analyses we used a measure that aggregates the contributions of Big 5 personality traits to healthy aging: a “vital personality” score. Methods Data came from two population-based longitudinal cohort studies, one based in New Zealand and the other in the UK, comprising over 6000 study members across two generations, and spanning an age range from birth to late life. Results Our analyses revealed three main findings: first, individuals with higher vital personality scores engaged in fewer health-risk behaviors, aged slower, and lived longer. Second, individuals’ vital personality scores were preceded by differences in early-life temperament and were relatively stable across adulthood, but also increased from young adulthood to midlife. Third, individuals with higher vital personality scores had children with similarly vital partners, promoted healthier behaviors in their children, and had children who grew up to have more vital personality scores themselves, for genetic and environmental reasons. Conclusion Our study shows how the health benefits associated with personality accrue throughout the life-course and across generations.
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Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor | 2021
J. Dowsett, E. Ferkingstad, L. J. H. Rasmussen, L. W. Thørner, M. K. Magnússon, ... Show all » K. Sugden, et al. « Hide
Communications Biology, 2021, 4(1), 655.
download pdf Our ref: RO765
Show abstract » Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR’s potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation.
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Changes to family structure, household composition and address among young New Zealanders: an update | 2021
McAnally, Helena M. Sligo, Judith L. Baxter, Joanne Tansley, Janine E. Bolton, ... Show all » Aroha E. Hancox, Robert J. « Hide
Kōtuitui: New Zealand Journal of Social Sciences Online, 2021, .
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Our ref: NZ100
Show abstract » In this article, we describe the life-time family structures, living arrangements, and residential mobility of 612 15-year-old New Zealanders and consider the differences in experiences of children born to younger and older mothers. All participants had a parent who is a member of the Dunedin Multidisciplinary Health and Development Study. Maternal age at the participant’s birth ranged from 16.3 to 41.0 years. Data on young people’s lifetime care arrangements, household composition and shifts were collected from their primary caregiver via a life history calendar. Fewer than half lived in a household consisting of two biological parents and only a fifth had lived in a household consisting of only nuclear family members for all 15 years. Most also experienced multiple changes of address (median 6, range 1–27). Those born to older parents tended to have fewer changes to care arrangements and family structures but most young people experienced a substantial degree of change across their lives. These data indicate that complexity and change are normal in young New Zealanders’ living arrangements. We argue that conventional ideas about family structure should be re-examined.
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Linking stressful life events and chronic inflammation using suPAR (soluble urokinase plasminogen activator receptor) | 2021
Bourassa, K. J. Rasmussen, L. J. H. Danese, A. Eugen-Olsen, J. Harrington, ... Show all » H. Houts, R. Poulton, R. Ramrakha, S. Sugden, K. Williams, B. Moffitt, T. E. Caspi, A. « Hide
Brain Behavior and Immunity, 2021, .
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Our ref: RO764
Show abstract » Stressful life events have been linked to declining health, and inflammation has been proposed as a physiological mechanism that might explain this association. Using 828 participants from the Dunedin Longitudinal Study, we tested whether people who experienced more stressful life events during adulthood would show elevated systemic inflammation when followed up in midlife, at age 45. We studied three inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. Stressful life events were not associated with CRP or IL-6. However, people who experienced more stressful life events from age 38 to 44 had elevated suPAR at age 45, and had significantly greater increases in suPAR from baseline to follow-up across the same period. When examining stressful life events across the lifespan, both adverse childhood experiences (ACEs) and adult stressful life events were independently associated with suPAR at age 45. ACEs moderated the association of adult stressful life events and suPAR at age 45-children with more ACEs showed higher suPAR levels after experiencing stressful life events as adults. The results suggest systemic chronic inflammation is one physiological mechanism that could link stressful life events and health, and support the use of suPAR as a useful biomarker for such research.
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Do socially isolated children become socially isolated adults? | 2021
Lay-Yee, Roy; Matthews, Timothy; Moffitt, Terrie; Poulton, Richie; Caspi, ... Show all » Avshalom; Milne, Barry. « Hide
Advances in Life Course Research, 2021, .
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Our ref: RO763
Show abstract » Social isolation - the lack of social contacts in number and frequency – has been shown to have a negative impact on health and well-being. Using group-based trajectory analysis of longitudinal data from a New Zealand birth cohort, we created a typology of social isolation based on onset during the life course and persistence into adulthood. We then characterized each type according to risk factors related to family environment and child behavior that have been shown previously to be associated with social isolation. Based on fit statistics and distinctness of trajectories we considered the four-class model to be the most appropriate: (1) ‘never isolated’ (71.6 % of the cohort), (2) ‘adult only’ (10.1 %), (3) ‘child only’ (14.3 %), and (4) ‘persistent isolation’ (4.0 %). Family-environmental factors – i.e. having a teen-aged mother, having a single parent, frequent changes in residence, or maltreatment – tended to be associated with both child and adult onset and persistence of social isolation, whereas child-behavioral factors – i.e. self-control or internalizing symptoms – applied more to the child onset of social isolation. Sensitivity analyses using empirically defined groups – based on 15 % ‘cut-offs’ for isolation in childhood and adulthood - produced similar life-course groupings and similar associations. Our findings provide insights into the development of social isolation and demonstrate the changeability of social isolation across almost four decades of the life span. They also suggest family-based and child-based interventions could address child onset and the persistence of social isolation into adulthood.
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Resource profile and user guide of the Polygenic Index Repository | 2021
Becker, J. Burik, C. A. P. Goldman, G. Wang, N. Jayashankar, ... Show all » H. Bennett, M. Belsky, D. W. Karlsson Linner, R. Ahlskog, R. Kleinman, A. Hinds, D. A. andMe Research, Group Caspi, A. Corcoran, D. L. Moffitt, T. E. Poulton, R. Sugden, K. Williams, B. S. Harris, K. M. Steptoe, A. Ajnakina, O. Milani, L. Esko, T. Iacono, W. G. McGue, M. Magnusson, P. K. E. Mallard, T. T. Harden, K. P. Tucker-Drob, E. M. Herd, P. Freese, J. Young, A. Beauchamp, J. P. Koellinger, P. D. Oskarsson, S. Johannesson, M. Visscher, P. M. Meyer, M. N. Laibson, D. Cesarini, D. Benjamin, D. J. Turley, P. Okbay, A. « Hide
Nature Human Behaviour, 2021, .
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Our ref: RO762
Show abstract » Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs' prediction accuracies, we constructed them using genome-wide association studies-some not previously published-from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the 'additive SNP factor'. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.
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Long-term Neural Embedding of Childhood Adversity in a Population-Representative Birth Cohort Followed for 5 Decades | 2021
Gehred, M. Z. Knodt, A. R. Ambler, A. Bourassa, K. J. Danese, ... Show all » A. Elliott, M. L. Hogan, S. Ireland, D. Poulton, R. Ramrakha, S. Reuben, A. Sison, M. L. Moffitt, T. E. Hariri, A. R. Caspi, A. « Hide
Biological Psychiatry, 2021, 90(3), 182-193.
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Our ref: RO761
Show abstract » BACKGROUND: Childhood adversity has been previously associated with alterations in brain structure, but heterogeneous designs, methods, and measures have contributed to mixed results and have impeded progress in mapping the biological embedding of childhood adversity. We sought to identify long-term differences in structural brain integrity associated with childhood adversity. METHODS: Multiple regression was used to test associations between prospectively ascertained adversity during childhood and adversity retrospectively reported in adulthood with structural magnetic resonance imaging measures of midlife global and regional cortical thickness, cortical surface area, and subcortical gray matter volume in 861 (425 female) members of the Dunedin Study, a longitudinal investigation of a population-representative birth cohort. RESULTS: Both prospectively ascertained childhood adversity and retrospectively reported adversity were associated with alterations in midlife structural brain integrity, but associations with prospectively ascertained childhood adversity were consistently stronger and more widely distributed than associations with retrospectively reported childhood adversity. Sensitivity analyses revealed that these associations were not driven by any particular adversity or category of adversity (i.e., threat or deprivation) or by childhood socioeconomic disadvantage. Network enrichment analyses revealed that these associations were not localized but were broadly distributed along a hierarchical cortical gradient of information processing. CONCLUSIONS: Exposure to childhood adversity broadly is associated with widespread differences in midlife gray matter across cortical and subcortical structures, suggesting that biological embedding of childhood adversity in the brain is long lasting, but not localized. Research using retrospectively reported adversity likely underestimates the magnitude of these associations. These findings may inform future research investigating mechanisms through which adversity becomes embedded in the brain and influences mental health and cognition.
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Autistic traits are associated with faster pace of aging: Evidence from the Dunedin study at age 45 | 2021
Mason, D. Ronald, A. Ambler, A. Caspi, A. Houts, ... Show all » R. Poulton, R. Ramrakha, S. Wertz, J. Moffitt, T. E. Happe, F. « Hide
Autism Research, 2021, .
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Our ref: RO760
Show abstract » Growing evidence indicates that the defining characteristics of autism spectrum disorder (ASD) are distributed throughout the general population; hence, understanding the correlates of aging in people with high autistic traits could shed light on ASD and aging. 915 members of the Dunedin longitudinal birth cohort completed a measure of autistic traits at age 45. A composite measure of the "pace of aging" was derived by tracking the decline in 19 biomarkers across ages 26, 32, 38, and 45 years. Facial age was also assessed. Reports of perceived health were collected from participants themselves, informants, and interviewers. Higher self-reported autistic traits significantly correlated with a faster pace of aging, older facial age, and poorer self-, informant-, and interviewer-rated health. After control for sex, SES and IQ, autistic traits were significantly associated with each variable: pace of aging (beta = 0.09), facial age (beta = 0.08), self- (beta = -0.15), informant (beta = -0.12), and interviewer-rated (beta = -0.17) health. Autistic traits measured at age 45 are associated with faster aging. Participants with high autistic traits appear to be more vulnerable to poor health outcomes, as previously reported for those clinically diagnosed with ASD. Therefore, autistic traits may have important health implications. Replicating these findings in samples of autistic people is needed to identify the mechanism of their effect on aging and physical health to improve outcomes for those with ASD diagnoses or high autistic traits. LAY SUMMARY: The role that autistic traits have in relation to health outcomes has not been investigated. We looked at how physical health and aging (measured with self-reported questions and decline in multiple biological measures) were related to autistic traits (measured with a questionnaire, at age 45). We found that higher autistic traits were associated with poorer reports of physical health, and a faster pace of aging. This suggests that both those with autism and those with higher autistic traits may be more likely to experience poorer health outcomes.
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Understanding the data-sharing debate in the context of Aotearoa/New Zealand: a narrative review on the perspectives of funders, publishers/journals, researchers, participants and Māori collectives | 2021
Reeves, Jane; Treharne, Gareth J.; Theodore, Reremoana; Edwards, Will; Ratima, ... Show all » Mihi; Poulton, Richie. « Hide
Kōtuitui: New Zealand Journal of Social Sciences Online, 2021, 1-23.
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Our ref: NZ99
Show abstract » This review outlines current debates about the sharing of research data, with a focus on relevance for Aotearoa/New Zealand. Recent years have seen increasingly frequent calls for public sharing of data from funders and publishers/journals in particular. Past research has suggested that researchers tend to agree that any detriments of data-sharing are outweighed by benefits for transparency and progress. We summarise trends across past research into perspectives of funders, publishers/journals, and researchers on data-sharing before raising three considerations. Firstly, past research on data-sharing has tended to overlook the potential implications of data-sharing for participants. We review the small body of research on participant perspectives. This research has conceptualised participants as a homogenous group without theorising how participants make sense of data-sharing. Secondly, perspectives on data-sharing vary depending on the methodology being applied, and we raise some specific considerations when datasharing is proposed in long-term longitudinal research such as the Dunedin Study. Thirdly, Indigenous perspectives on data-sharing must be central to all research into data-sharing with any of the stakeholder groups, and we review existing research on data sovereignty in relation to data-sharing in Aotearoa/New Zealand and globally. We conclude by summarising a series of tensions between stakeholders in the data-sharing debate.
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Genetic Association Study of Childhood Aggression across raters, instruments and age | 2021
Ip, Hill F. Van Der Laan, Camiel M. Krapohl, Eva M. L. Brikell, Isabell Cristina, ... Show all » Sánchez-Mora Nolte, Ilja M. St Pourcain, Beate Bolhuis, Koen Palviainen, Teemu Zafarmand, Hadi Colodro-Conde, Lucía Gordon, Scott Zayats, Tetyana Aliev, Fazil Jiang, Chang Wang, Carol A. Saunders, Gretchen Karhunen, Ville Hammerschlag, Anke R. Adkins, Daniel E. Border, Richard Peterson, Roseann E. Prinz, Joseph A. Thiering, Elisabeth Seppälä, Ilkka Natàlia, Vilor-Tejedor Ahluwalia, Tarunveer S. Day, Felix R. Hottenga, Jouke-Jan Allegrini, Andrea G. Rimfeld, Kaili Chen, Qi Lu, Yi Martin, Joanna Soler Artigas, María Rovira, Paula Bosch, Rosa Español, Gemma Ramos Quiroga, Josep Antoni Neumann, Alexander Ensink, Judith Grasby, Katrina Morosoli, José J. Tong, Xiaoran Marrington, Shelby Middeldorp, Christel Scott, James G. Vinkhuyzen, Anna Shabalin, Andrey A. Corley, Robin Evans, Luke M. Sugden, Karen Alemany, Silvia Sass, Lærke Vinding, Rebecca Ruth, Kate Tyrrell, Jess Davies, Gareth E. Ehli, Erik A. Hagenbeek, Fiona A. De Zeeuw, Eveline Van Beijsterveldt, Toos C. E. M. Larsson, Henrik Snieder, Harold Verhulst, Frank C. Amin, Najaf Whipp, Alyce M. Korhonen, Tellervo Vuoksimaa, Eero Rose, Richard J. Uitterlinden, André G. Heath, Andrew C. Madden, Pamela Haavik, Jan Harris, Jennifer R. Helgeland, Øyvind Johansson, Stefan Knudsen, Gun Peggy S. Njolstad, Pal Rasmus Lu, Qing Rodriguez, Alina Henders, Anjali K. Mamun, Abdullah Najman, Jackob M. Brown, Sandy Hopfer, Christian Krauter, Kenneth Reynolds, Chandra Smolen, Andrew Stallings, Michael Wadsworth, Sally Wall, Tamara L. Silberg, Judy L. Miller, Allison Keltikangas-Järvinen, Liisa Hakulinen, Christian Pulkki-Råback, Laura Havdahl, Alexandra Magnus, Per Raitakari, Olli T. Perry, John R. B. Llop, Sabrina Lopez-Espinosa, Maria-Jose Bønnelykke, Klaus Bisgaard, Hans Sunyer, Jordi Lehtimäki, Terho Arseneault, Louise Standl, Marie Heinrich, Joachim Boden, Joseph Pearson, John Horwood, L. John Kennedy, Martin Poulton, Richie Eaves, Lindon J. Maes, Hermine H. Hewitt, John Copeland, William E. Costello, Elizabeth J. Williams, Gail M. Wray, Naomi Järvelin, Marjo-Riitta McGue, Matt Iacono, William Caspi, Avshalom Moffitt, Terrie E. Whitehouse, Andrew Pennell, Craig E. Klump, Kelly L. Burt, S. Alexandra Dick, Danielle M. Reichborn-Kjennerud, Ted Martin, Nicholas G. Medland, Sarah E. Vrijkotte, Tanja Kaprio, Jaakko Tiemeier, Henning Davey Smith, George Hartman, Catharina A. Oldehinkel, Albertine J. Casas, Miquel Ribasés, Marta Lichtenstein, Paul Lundström, Sebastian Plomin, Robert Bartels, Meike Nivard, Michel G. Boomsma, Dorret I. « Hide
Translational Psychiatry, 2021, .
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Show abstract » Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data – i.e. within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE=0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P=1.6E-06), PCDH7 (P=2.0E-06) and IPO13 (P=2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg =0.46 between self- and teacher-assessment to rg =0.81 between mother- and teacher-assessment. We obtained moderate to strong rg’s with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg| : 0.19 – 1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg =~ −0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg| : 0.46 – 0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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