The Dunedin Study - DMHDRU

Publications

All peer reviewed publications are listed below.

Displaying page 2 of 22.

General functional connectivity: Shared features of resting-state and task fMRI drive reliable and heritable individual differences in functional brain networks | 2019
Maxwell L. Elliott, Annchen R. Knodt, Megan Cooke, M. Justin Kim, Tracy R. Melzer, ... Show all » Ross Keenan, David Ireland, Sandhya Ramrakha, Richie Poulton, Avshalom Caspi, Terrie E. Moffitt, Ahmad R. Hariri « Hide
NeuroImage, 2019, 189 516-532.
https://doi.org/10.1016/j.neuroimage.2019.01.068
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Our ref: RO719
Show abstract » Intrinsic connectivity, measured using resting-state fMRI, has emerged as a fundamental tool in the study of the human brain. However, due to practical limitations,
many studies do not collect enough resting-state data to generate reliable measures of intrinsic connectivity necessary for studying individual differences. Here we
present general functional connectivity (GFC) as a method for leveraging shared features across resting-state and task fMRI and demonstrate in the Human Connectome
Project and the Dunedin Study that GFC offers better test-retest reliability than intrinsic connectivity estimated from the same amount of resting-state data
alone. Furthermore, at equivalent scan lengths, GFC displayed higher estimates of heritability than resting-state functional connectivity. We also found that predictions
of cognitive ability from GFC generalized across datasets, performing as well or better than resting-state or task data alone. Collectively, our work suggests that GFC can improve the reliability of intrinsic connectivity estimates in existing datasets and, subsequently, the opportunity to identify meaningful correlates of individual differences in behavior. Given that task and resting-state data are often collected together, many researchers can immediately derive more reliable measures of intrinsic connectivity through the adoption of GFC rather than solely using resting-state data. Moreover, by better capturing heritable variation in intrinsic connectivity, GFC represents a novel endophenotype with broad applications in clinical neuroscience and biomarker discovery.

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A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains | 2019
Elliott, M. L. Belsky, D. W. Anderson, K. Corcoran, D. L. Ge, ... Show all » T. Knodt, A. Prinz, J. A. Sugden, K. Williams, B. Ireland, D. Poulton, R. Caspi, A. Holmes, A. Moffitt, T.E. Hariri, A. R. « Hide
Cerebal Cortex, 2019, 1-9.
https://doi.org/10.1093/cercor/bhy219
download pdf Our ref: RO706
Show abstract » People who score higher on intelligence tests tend to have larger brains. Twin studies suggest the same genetic factors influence both brain size and intelligence. This has led to the hypothesis that genetics influence intelligence partly by contributing to development of larger brains. We tested this hypothesis with molecular genetic data using discoveries from a genome-wide association study (GWAS) of educational attainment, a correlate of intelligence. We analyzed genetic, brain imaging, and cognitive test data from the UK Biobank, the Dunedin Study, the Brain Genomics Superstruct Project (GSP), and the Duke Neurogenetics Study (DNS) (combined N=8,271). We measured genetics using polygenic scores based on published GWAS. We conducted meta-analysis to test associations among participants' genetics, total brain volume (i.e., brain size), and cognitive test performance. Consistent with previous findings, participants with higher polygenic scores achieved higher scores on cognitive tests, as did participants with larger brains. Participants with higher polygenic scores also had larger brains. We found some evidence that brain size partly mediated associations between participants' education polygenic scores and their cognitive test performance. Effect-sizes were larger in the population-based UK Biobank and Dunedin samples than in the GSP and DNS samples. Sensitivity analysis suggested this effect-size difference partly reflected restricted range of cognitive performance in the GSP and DNS samples. Recruitment and retention of population-representative samples should be a priority for neuroscience research. Findings suggest promise for studies integrating GWAS discoveries with brain imaging data to understand neurobiology linking genetics with individual differences in cognitive performance.
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Childhood IQ predicts age-38 oral disease experience and service-use | 2019
Thomson WM, Broadbent JM, Caspi A, Poulton R, Moffitt TE
Community Dentistry and Oral Epidemiology, 2019, 47(3), 252-258.
https://doi.org/10.1111/cdoe.12451
Our ref: RO718
Show abstract » OBJECTIVES:
Given that people with higher intelligence have been shown to live longer, enjoy better health and have more favourable health behaviours, we investigated the association between childhood IQ and a range of important dental health and service-use indicators at age 38.

METHODS:
Long-standing prospective study of a complete birth cohort, with childhood IQ (assessed at ages 7, 9, 11 and 13 years) used to allocate participants (N = 818) to one of four ordinal categories of childhood IQ.

RESULTS:
There were distinct and consistent gradients by childhood IQ in almost all of the dental caries experience measures (with the exception of filled teeth) whereby each was most severe in the lowest child IQ category and least severe in the highest; the exception was the mean FT score, for which there was no discernible gradient. Indicators of self-care and periodontal disease experience showed similar gradients, and multivariate modelling using the continuous IQ score confirmed the observed patterns.

CONCLUSIONS:
Childhood cognitive function is a key determinant of oral health and dental service-use by midlife, with those of lower cognitive capacity as children likely to have poorer oral health, less favourable oral health-related beliefs, and more detrimental self-care and dental visiting practices by age 38. There is a need to shape dental clinical services and public health interventions so that people with the poorest cognitive function do not continue to be disadvantaged.

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Establishing a generalized polyepigenetic biomarker for tobacco smoking | 2019
Sugden K, Hannon E J, Arseneault L, Belsky DW, Broadbent JM, ... Show all » Corcoran DL Hancox RJ Houts RM Moffitt TE Poulton R Prinz JA Thomson WM, Williams BS Wong CCY Mill J Caspi A « Hide
Translational Psychiatry, 2019, 9 .
https://doi.org/10.1038/s41398-019-0430-9
Our ref: RO717
Show abstract » Large-scale epigenome-wide association meta-analyses have identified multiple ‘signatures’’ of smoking. Drawing on these findings, we describe the construction of a polyepigenetic DNA methylation score that indexes smoking behavior and that can be utilized for multiple purposes in population health research. To validate the score, we use data from two birth cohort studies: The Dunedin Longitudinal Study, followed to age-38 years, and the Environmental Risk Study, followed to age-18 years. Longitudinal data show that changes in DNA methylation accumulate with increased exposure to tobacco smoking and attenuate with quitting. Data from twins discordant for smoking behavior show that smoking influences DNA methylation independently of genetic and environmental risk factors. Physiological data show that changes in DNA methylation track smoking-related changes in lung function and gum health over time. Moreover, DNA methylation changes predict corresponding changes in gene expression in pathways related to inflammation, immune response, and cellular trafficking. Finally, we present prospective data about the link between adverse childhood experiences (ACEs) and epigenetic modifications; these findings document the importance of controlling for smoking-related DNA methylation changes when studying biological embedding of stress in life-course research. We introduce the polyepigenetic DNA methylation score as a tool both for discovery and theory-guided research in epigenetic epidemiology
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Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis | 2019
Hartwig FP, Davies NM, Horta BL, Ahluwalia TS, Bisgaard H, ... Show all » Bønnelykke K, Caspi A, Moffitt TE, Poulton R, Sajjad A, Tiemeier HW, Dalmau-Bueno A, Guxens M, Bustamante M, Santa-Marina L, Parker N, Paus T, Pausova Z, Lauritzen L, Schnurr TM, Michaelsen KF, Hansen T, Oddy W, Pennell CE, Warrington NM, Davey Smith G, Victora CG « Hide
International Journal of Epidemiology, 2019, 48(1), 45–57.
https://doi.org/10.1093/ije/dyy273
Our ref: RO715
Show abstract » BACKGROUND:
Accumulating evidence suggests that breastfeeding benefits children's intelligence, possibly due to long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial.

METHODS:
We investigated this gene × environment interaction through a collaborative effort. The primary analysis involved >12 000 individuals and used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores.

RESULTS:
There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e. difference between genetic groups of the difference in IQ Z scores comparing ever with never breastfed individuals) of 0.12[(95% confidence interval (CI): -0.19; 0.43] and 0.06 (95% CI: -0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with ≥5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: -0.06; 1.06) and 0.14 (95% CI: -0.10; 0.38), respectively, and 0.27 (95% CI: -0.28; 0.82) and -0.01 (95% CI: -0.19; 0.16) for the rs1535 variant.

CONCLUSIONS:
Our findings did not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, subgroup analysis suggested that breastfeeding may supply LC-PUFAs requirements for cognitive development if breastfeeding lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and further improve our understanding on the breastfeeding × FADS2 interaction.

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Association of Childhood Lead Exposure With Adult Personality Traits and Lifelong Mental Health | 2019
Reuben, Aaron Schaefer, Jonathan Moffitt, Terrie Broadbent, Jonathan Harrington, ... Show all » Honalee Houts, Renate Ramrakha, Sandhya Poulton, Richie Caspi, Avshalom « Hide
JAMA Psychiatry, 2019, 76(4), 418-425.
10.1001/jamapsychiatry.2018.4192
download pdf Our ref: RO714
Show abstract » Importance: Millions of adults now entering middle age were exposed to high levels of lead, a developmental neurotoxin, as children. Although childhood lead exposure has been linked to disrupted behavioral development, the long-term consequences for adult mental and behavioral health have not been fully characterized. Objective: To examine whether childhood lead exposure is associated with greater psychopathology across the life course and difficult adult personality traits. Design, setting, and participants: This prospective cohort study was based on a population-representative birth cohort of individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, the Dunedin Multidisciplinary Health and Development Study. Members were followed up in December 2012 when they were 38 years of age. Data analysis was performed from March 14, 2018, to October 24, 2018. Exposures: Childhood lead exposure ascertained as blood lead levels measured at 11 years of age. Blood lead levels were unrelated to family socioeconomic status. Main outcomes and measures: Primary outcomes were adult mental health disorder symptoms assessed through clinical interview at 18, 21, 26, 32, and 38 years of age and transformed through confirmatory factor analysis into continuous measures of general psychopathology and internalizing, externalizing, and thought disorder symptoms (all standardized to a mean [SD] of 100 [15]) and adult personality assessed through informant report using the Big Five Personality Inventory (assessing neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) at 26, 32, and 38 years of age (all scores standardized to a mean [SD] of 0 [1]). Hypotheses were formulated after data collection; an analysis plan was posted in advance. Results: Of 1037 original study members, 579 (55.8%) were tested for lead exposure at 11 years of age (311 [53.7%] male). The mean (SD) blood lead level was 11.08 (4.96) μg/dL. After adjusting for study covariates, each 5-μg/dL increase in childhood blood lead level was associated with a 1.34-point increase (95% CI, 0.11-2.57; P = .03) in general psychopathology, driven by internalizing (b = 1.41; 95% CI, 0.19-2.62; P = .02) and thought disorder (b = 1.30; 95% CI, 0.06-2.54; P = .04) symptoms. Each 5-μg/dL increase in childhood blood lead level was also associated with a 0.10-SD increase in neuroticism (95% CI, 0.02-0.08; P = .02), a 0.09-SD decrease in agreeableness (95% CI, -0.18 to -0.01; P = .03), and a 0.14-SD decrease in conscientiousness (95% CI, -0.25 to -0.03; P = .01). There were no statistically significant associations with informant-rated extraversion (b = -0.09; 95% CI, -0.17 to 0.004; P = .06) and openness to experience (b = -0.07; 95% CI, -0.17 to 0.03; P = .15). Conclusions and relevance: In this multidecade, longitudinal study of lead-exposed children, higher childhood blood lead level was associated with greater psychopathology across the life course and difficult adult personality traits. Childhood lead exposure may have long-term consequences for adult mental health and personality
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Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood | 2019
Rasmussen, L.J.H., Moffitt, T.E., Eugen-Olsen, ... Show all » J., Belsky, D.W., Danese, A., Harrington, H., Houts R.M., Poulton, R., Sugden, K., Williams, B., Caspi, A. « Hide
Journal of Child Psychology and Psychiatry, 2019, 60(2), 199-208.
10.1111/jcpp.12928
download pdfLink to full publication »
Our ref: RO708
Show abstract » Background:Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it isunknown whether these risk factors are associated with increased adult levels of the chronic inflammation markersoluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposureto risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-reactive protein (CRP).Methods:Prospective study of a population-representa-tive 1972–1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants toage 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhoodexperiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measuredas suPAR and high-sensitivity CRP (hsCRP).Results:Participants with available plasma samples at age 38 wereincluded (N=837, 50.5% male). suPAR (mean 2.40 ng/ml;SD0.91) was positively correlated with hsCRP (r0.15,p<.001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lowerIQ, or had poorer self-control showed elevated adult suPAR. When the five childhood risks were aggregated into aCumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk wasassociated with higher suPAR (b0.10; SE 0.03;p=.002). Cumulative Childhood Risk predicted elevated suPAR, aftercontrolling for hsCRP (b0.18; SE 0.03;p<.001).Conclusions:Exposure to more childhood risk factors wasassociated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhoodrisk to adult inflammatory burden.
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Does physical fitness enhance lung function in children and young adults? | 2018
Robert J. Hancox, Finn Rasmussen
European Respiratory Journal, 2018, 51(2), .
https://doi.org/10.1183/13993003.01374-2017
Our ref: RO713
Show abstract » Although physical activity is important for lung health, it is unclear whether physical fitness influences lung function. We investigated associations between lung function and fitness in two population-based cohort studies of children and young adults.

Aerobic fitness was measured using a maximal cycle ergometer test at ages 9, 15, 21 and 29 years in Odense, Denmark and using a submaximal cycle test at ages 15, 26, 32 and 38 years in Dunedin, New Zealand.

Aerobic fitness was positively associated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in cross-sectional analyses at all ages in both cohorts, independently of height, weight, sex, asthma and smoking. Each standard deviation difference in fitness was associated with 2–3% predicted higher values of FEV1 and FVC. Improvements in fitness during childhood and adolescence were associated with growth in lung volumes in longitudinal analyses. These associations tended to be stronger in males than females. No longitudinal associations were found after peak adult lung function had been attained. Fitness was not significantly associated with FEV1/FVC ratios.

Aerobic fitness is positively associated with lung volumes. Improving fitness during childhood and adolescence is associated with greater adult lung volumes, but not with airway calibre.

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Intergenerational changes in adolescents’ physical fitness and weight in New Zealand | 2018
McAnally HM, Reeves LM, Sligo JL, Hancox RJ
The New Zealand medical journal, 2018, 131(1482), 16-28.
Link to full publication »
Our ref: NZ95
Show abstract » AIMS:
This research examines fitness and body weight in two cohorts of adolescents, to determine continuity and changes in these measures across two generations.

METHODS:
Height, weight and fitness were measured in a population-based cohort of 15 year-olds in 1986/7 (Dunedin Study, n=968). The same measures were obtained for their 15-16 year-old children between 2007 and 2015 (Next Generation Study, n=343). Fitness was defined as maximal aerobic capacity (V'O2max). Height and weight were measured in all participants and fitness was adjusted for weight (V'O2max/kg).

RESULTS:
The Next Generation participants were, on average, heavier than the Dunedin Study participants had been, and had higher body mass index values (kg/m2). Unadjusted V'O2max values for boys did not differ between generations, but were lower in Next Generation girls compared to Dunedin Study girls. For both sexes, the Next Generation participants had lower weight-adjusted V'O2max values than the Dunedin Study participants. Compared to their parents, weight-adjusted V'O2max values were approximately 25% lower in girls and 15% lower in boys.

CONCLUSIONS:
Overall adolescents today appear to be less fit and heavier than their parents were at the same age. The decline in fitness over a generation is particularly evident in adolescent girls, although boys also have lower levels of fitness once body weight has been taken into account.

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Periodontitis and multiple markers of cardiometabolic risk in the fourth decade: A cohort study | 2018
Shearer, D. M. Thomson, W. M. Cameron, C. M. Ramrakha, S. Wilson, ... Show all » G. Wong, T. Y. Williams, M. J. A. McLean, R. Theodore, R. Poulton, R. « Hide
Community Dentistry and Oral Epidemiology, 2018, 46(6), 615-623.
download pdfLink to full publication »
Our ref: RO712
Show abstract » OBJECTIVES: To examine associations between periodontitis at ages 32 and 38 and a range of early cardiometabolic risk biomarkers at age 38. METHODS: Periodontal probing depth and bleeding on probing data collected during the age-32 and age-38 assessments in the Dunedin Multidisciplinary Health and Development Study were used to quantify periodontal inflammatory load. Retinal microvascular abnormalities, endothelial dysfunction, and metabolic syndrome data were collected during the age-38 assessment. Regression models were used to examine associations between these cardiometabolic risk markers and (1) the inflammatory load at age 38 and (2) the change in inflammatory load between ages 32 and 38. RESULTS: Periodontal inflammatory load was recorded for 890 Study members at age 32, 891 at age 38, and 856 at both ages. Retinal vessel data were available for 922, endothelial dysfunction data for 909 and metabolic syndrome data for 905 at age 38. Neither the inflammatory load of periodontitis at 38 nor the changes in inflammatory load 32-38 were found to be associated with any of the three cardiometabolic risk markers. CONCLUSIONS: Periodontitis was not associated with markers of cardiometabolic risk at this relatively early stage in the life course. It is possible that any influence of periodontitis on cardiometabolic health develops later in life, or periodontitis is not involved in the putative causal chain comprising systemic inflammation, cardiometabolic risk markers, and subsequent cardiovascular risk.
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Genetic analysis of social mobility in five longitudinal studies | 2018
Belsky, D.W. Domingue, B.W Wedow, R Arseneault, L. Boardman, ... Show all » J Caspi, A. Conley, D Fletcher, J.M Freese, J Herd, P Moffitt, T. E Poulton, R. Sicinski, K Wertz, J. Mullan Harris, K « Hide
PNAS (Proceedings of the National Academy of Sciences of the USA), 2018, 115(13), E7275-E7284.
https://doi.org/10.1073/pnas.1817958115
Our ref: RO702
Show abstract » A summary genetic measure, called a “polygenic score,” derived from a genome-wide association study (GWAS) of education can modestly predict a person’s educational and economic success. This prediction could signal a biological mechanism: Educationlinked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents’ position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother’s polygenic score predicted her child’s attainment over and above the child’s own polygenic score, suggesting parents’ genetics can also affect their children’s attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals’ family-oforigin environments and their social mobility.
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Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior | 2018
Wertz, J. Caspi, A. Belsky, D. W. Beckley, A. L. Arseneault, ... Show all » L. Barnes, J. C. Corcoran, D. L. Hogan, S. Houts, R. Morgan, N. Odgers, C. L. Prinz, Joseph A. Sugden, K. Williams, B.S. Poulton, R. Moffitt, T. E « Hide
Psychological Science, 2018, 29(5), 791-803.
download pdfLink to full publication »
Our ref: RO703
Show abstract » Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.
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Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing? | 2018
Belsky, D. W. Moffitt, T.E. Cohen, A.A. Corcoran, D. L. Levine, ... Show all » M.E. Prinz, J. A. Schaefer, J. Sugden, K. Williams, B. Poulton, R. Caspi, A. « Hide
American Journal of Epidemiology, 2018, 187(6), 1220-1230.
http://dx.doi.org/10.1093/aje/kwx346
Our ref: RO700
Show abstract » The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such “gero-protective” therapies in humans, outcome measures are needed that can assess extension of disease-free lifespan. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented seven methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study. We studied telomere-length and erosion, three epigenetic-clocks and their ticking rates, and three biomarker-composites, 11 measures in total. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes gero-protective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-CpG epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect-sizes were modest. Results suggests that various proposed approaches to quantifying biological aging may not measure the same aspects of the aging process. Further systematic evaluation and refinement of measures of biological aging is needed to furnish outcomes for geroprotector trials.
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Analysis of DNA Methylation in Young People: Limited Evidence for an Association Between Victimization Stress and Epigenetic Variation in Blood | 2018
Marzi, S. J. Sugden, K. Arseneault, L. Belsky, D. W. Burrage, ... Show all » J. Corcoran, D. L. Danese, A. Fisher, H. L. Hannon, E. Moffitt, T. E. Odgers, C. L. Pariante, C. Poulton, R. Williams, B. S. Wong, C. C. Y. Mill, J. Caspi, A. « Hide
American Journal of Psychiatry, 2018, 175(6), 517-529.
https://doi.org/10.1176/appi.ajp.2017.17060693
Our ref: RO705
Show abstract » Objective:DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become “embedded” in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation.Method:The authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994–1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization were ascertained in childhood and adolescence (including physical, sexual, and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-victimization; and crime).Results:Epigenome-wide analyses of polyvictimization across childhood and adolescence revealed few significant associations with DNA methylation in peripheral blood at age 18, but these analyses were confounded by tobacco smoking and/or did not survive co-twin control tests. Secondary analyses of specific forms of victimization revealed sparse associations with DNA methylation that did not replicate across different operationalizations of the same putative victimization experience. Hypothesis-driven analyses of six candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted associations with DNA methylation in probes annotated to these genes.Conclusions:Findings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people. We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress.
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The high societal costs of childhood conduct problems: evidence from administrative records up to age 38 in a longitudinal birth cohort | 2018
Rivenbark, Joshua G. Odgers, Candice L. Caspi, Avshalom Harrington, HonaLee Hogan, ... Show all » Sean Houts, Renate M. Poulton, Richie Moffitt, Terrie E. « Hide
Journal of Child Psychology and Psychiatry, 2018, 59(6), 703-710.
https://doi.org/10.1111/jcpp.12850
Our ref: RO701
Show abstract » Children with conduct problems that persist into adulthood are at increased risk for future behavioral, health, and social problems. However, the longer term public service usage among these children has not been fully documented. To aid public health and intervention planning, adult service usage across criminal justice, health care, and social welfare domains is compared among all individuals from a representative cohort who followed different conduct problem trajectories from childhood into adulthood. Participants are from the Dunedin Multidisciplinary Health and Development Study, a prospective, representative cohort of consecutive births (N = 1,037) from April 1972 to March 1973 in Dunedin, New Zealand. Regression analyses were used to compare levels of public service usage up to age 38, gathered via administrative and electronic medical records, between participants who displayed distinct subtypes of childhood conduct problems (low, childhood-limited, adolescent-onset, and life-course persistent). Children exhibiting life-course persistent conduct problems used significantly more services as adults than those with low levels of childhood conduct problems. Although this group comprised only 9.0% of the population, they accounted for 53.3% of all convictions, 15.7% of emergency department visits, 20.5% of prescription fills, 13.1% of injury claims, and 24.7% of welfare benefit months. Half of this group (50.0%) also accrued high service use across all three domains of criminal justice, health, and social welfare services, as compared to only 11.3% of those with low conduct problems (OR = 7.27, 95% CI = 4.42–12.0). Conduct problems in childhood signal high future costs in terms of service utilization across multiple sectors. Future evaluations of interventions aimed at conduct problems should also track potential reductions in health burden and service usage that stretch into midlife.
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Association of childhood blood lead levels with criminal offending | 2018
Beckley, A. L. Caspi, A. Broadbent, J. Harrington, HL Houts, ... Show all » R. Poulton, R. Ramrakha, S. Reuben, A. Moffitt , T.E. « Hide
JAMA Pediatrics, 2018, 172(2), 166-173.
http://dx.doi.org/10.1001/jamapediatrics.2017.4005
Our ref: RO707
Show abstract » Importance  Lead is a neurotoxin with well-documented effects on health. Research suggests that lead may be associated with criminal behavior. This association is difficult to disentangle from low socioeconomic status, a factor in both lead exposure and criminal offending.Objective  To test the hypothesis that a higher childhood blood lead level (BLL) is associated with greater risk of criminal conviction, recidivism (repeat conviction), conviction for violent offenses, and variety of self-reported criminal offending in a setting where BLL was not associated with low socioeconomic status.Design, Setting, and Participants  A total of 553 individuals participated in a prospective study based on a population-representative cohort born between April 1, 1972, and March 31, 1973, from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (December 2012). Statistical analysis was performed from November 10, 2016, to September 5, 2017.Exposures  Blood lead level measured at age 11 years.Main Outcomes and Measures  Official criminal conviction cumulative to age 38 years (data collected in 2013), single conviction or recidivism, conviction for nonviolent or violent crime, and self-reported variety of crime types at ages 15, 18, 21, 26, 32, and 38 years.Results  Participants included 553 individuals (255 female and 298 male participants) who had their blood tested for lead at age 11 years. The mean (SD) BLL at age 11 years was 11.01 (4.62) μg/dL. A total of 154 participants (27.8%) had a criminal conviction, 86 (15.6%) had recidivated, and 53 (9.6%) had a violent offense conviction. Variety scores for self-reported offending ranged from 0 to 10 offense types at each assessment; higher numbers indicated greater crime involvement. Self-reported offending followed the well-established age-crime curve (ie, the mean [SD] variety of self-reported offending increased from 1.99 [2.82] at age 15 years to its peak of 4.24 [3.15] at age 18 years and 4.22 [3.02] at age 21 years and declined thereafter to 1.10 [1.59] at age 38 years). Blood lead level was a poor discriminator between no conviction and conviction (area under the curve, 0.58). Overall, associations between BLL and conviction outcomes were weak. The estimated effect of BLL was lower for recidivism than for single convictions and lower for violent offending than for nonviolent offending. Sex-adjusted associations between BLL reached statistical significance for only 1 of the 6 self-reported offending outcomes at age 15 years (r = 0.10; 95% CI, 0.01-0.18; P = .02).Conclusions and Relevance  This study overcomes past limitations of studies of BLL and crime by studying the association in a place and time where the correlation was not confounded by childhood socioeconomic status. Findings failed to support a dose-response association between BLL and consequential criminal offending.
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Non-suicidal self-injury and suicide attempts in a New Zealand birth cohort | 2017
Coppersmith, D. D. L. Nada-Raja, S. Beautrais, A. L.
Journal of Affective Disorders, 2017, 221 89-96.
10.1016/j.jad.2017.06.029
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Our ref: RO711
Show abstract » Background: Non-suicidal self-injury (NSSI) and suicide attempts are related, but distinct behaviors. The primary aim of the current study was to identify factors that distinguish those with different lifetime histories of selfinjury. A secondary aim was to test whether lifetime history of self-injury at age 26 predicted current suicide ideation at age 32.
Methods: Participants were 26 year olds from a large birth cohort with a lifetime history of no self-injury (n = 466), a lifetime history of NSSI (n = 191), or a lifetime history of NSSI and a suicide attempt (NSSI+ SA; n = 52). They were compared on a history of psychiatric disorders, 12-month suicide ideation, lifetime history of childhood sexual abuse, and lifetime exposure to suicide.
Results: An anxiety disorder, a substance dependence disorder, suicide ideation, and a history of childhood sexual abuse distinguished the NSSI+ SA and NSSI only groups. Longitudinal results demonstrated that a history of NSSI predicted future suicide ideation after adjusting for other selected risk factors.
Limitations: The majority of analyses are cross-sectional which limits inferences about causality. The retrospective self-report for lifetime behavior could be subject to reporting biases.
Conclusions: Adults with a history of NSSI and adults with a history of NSSI and a suicide attempt are clinically distinct groups that are both at risk of future suicide ideation. Identifying and treating NSSI could be a key preventive factor in reducing subsequent suicide risk.

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Life-Course Relationship between Socioeconomic Circumstances and Timing of First Birth in a Birth Cohort | 2017
van Roode, T. Sharples, K. Dickson, N. Paul, C.
PLoS One, 2017, 12(1), e0170170.
10.1371/journal.pone.0170170
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Our ref: RO709
Show abstract » OBJECTIVES: This study examines the influence of socioeconomic circumstances in childhood (childhood SES) and adulthood (adult SES) on timing of first birth by age 37. METHODS: A longitudinal study of a 1972-1973 New Zealand birth cohort collected information on socioeconomic characteristics from age 3-32 and reproductive histories at 21, 26, 32 and 38; information on first birth was available from 978 of the original 1037. Relative Risks (RR) and 95% Confidence Intervals (CI) were calculated using Poisson regression to examine first live birth prior to age 21, from 21-25, from 26-31, and from 32-37, by socioeconomic characteristics at different ages. RESULTS: Overall, 68.5% of men had fathered a child and 75.9% of women had given birth, by age 37; with overall differences in parenthood to age 31 for men, and 37 for women evident by childhood SES. While parenthood by age 20 was strongly associated with lower childhood SES for both sexes, first entry into motherhood from 32-37 was more likely with higher adult SES at age 32 (RR = 1.8, 95% CI 1.1-3.0 for medium and RR = 1.9, 95% CI 1.1-3.3 for high compared with low). Education also differientated age at parenthood, with those with higher education more likely to defer fatherhood past age 31, and motherhood past age 25 followed by a period of increased likelihood of motherhood for women with higher levels of education from age 32-37 (RR = 1.4, 95% CI 0.87-2.2 and RR = 1.7, 95% CI 1.1-2.6 for medium and high respectively compared with low). CONCLUSIONS: SES varies across the lifecourse, and SES at the time has the strongest association with first births at that time. Low childhood SES drives adolescent parenthood, with resulting cumulative differences in parenthood past age 30. Those with more education and higher adult SES are deferring parenthood but attempt to catch up in the mid to late thirties.
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How much atopy is attributable to common childhood environmental exposures? A population-based birth cohort study followed to adulthood | 2017
Shin HH., Lynch SJ., Gray AR., Sears MR., Hancox RJ.
International Journal of Epidemiology, 2017, 46(6), 2009-2016.
https://doi.org/10.1093/ije/dyx098
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Our ref: RO724
Show abstract » BACKGROUND:
The rising prevalence of atopic diseases implies a strong influence of environmental determinants. Epidemiological studies have identified several early life exposures that appear to influence the risk of developing atopic sensitization, but the combined influence of these exposures is unknown. We sought to estimate the proportion of atopy that could be attributed to common childhood exposures associated with atopic sensitization in adolescence and young adulthood.

METHODS:
Atopic sensitization was measured by skin-prick tests for common aeroallergens in a population-based New Zealand birth cohort at ages 13 and 32 years. The independent effects of previously identified risk and protective factors for atopic sensitization were assessed using multiple logistic regression. Population attributable fractions were calculated for atopic sensitization in childhood and adulthood.

RESULTS:
Tobacco smoke exposure, dog and cat ownership, nail-biting and thumb-sucking, attending pre-school day care, and household crowding were associated with a lower risk of atopic sensitization whereas breastfeeding was associated with a higher risk. Population attributable fractions for combined effects of these environmental factors suggest that they may account for 58% of atopic sensitization at age 13 and 49% at age 32 years.

CONCLUSIONS:
A substantial proportion of atopic sensitization appears to be attributable to common childhood environmental and lifestyle factors, and the influence of these exposures persists into adulthood. The absolute risks attributable to these exposures will be different in other cohorts and we cannot assume that these associations are necessarily causal. Nevertheless, the findings suggest that identifiable childhood environmental factors contribute substantially to atopic sensitization.

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Is low cognitive functioning a predictor or consequence of major depressive disorder? A test in two longitudinal birth cohorts | 2017
Schaefer, J. D. Scult, M. A. Caspi, A. Arseneault, L. Belsky, ... Show all » D. W. Hariri, A. R. Harrington, H. Houts, R. Ramrakha, S. Poulton, R. Moffitt, T. E. « Hide
Development and Psychopathology, 2017, 16 1-15.
https://doi.org/10.1017/S095457941700164X
download pdf Our ref: RO710
Show abstract » Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.
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Impact of early personal-history characteristics on the Pace of Aging: implications for clinical trials of therapies to slow aging and extend healthspan | 2017
Belsky, D. W., Caspi, A., Cohen, ... Show all » H. J., Kraus, W. E., Ramrakha, S., Poulton, R., Moffitt, T. E. « Hide
Aging Cell, 2017, 16(4), 644-651.
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Our ref: RO699
Show abstract » Therapies to extend healthspan are poised to move from laboratory animal models to human clinical trials. Translation from mouse to human will entail challenges, among them the multifactorial heterogeneity of human aging. To inform clinical trials about this heterogeneity, we report how humans’ pace of biological aging relates to personal-history characteristics. Because geroprotective therapies must be delivered by midlife to prevent age-related disease onset, we studied young-adult members of the Dunedin Study 1972–73 birth cohort (n = 954). Cohort members’ Pace of Aging was measured as coordinated decline in the integrity of multiple organ systems, by quantifying rate of decline across repeated measurements of 18 biomarkers assayed when cohort members were ages 26, 32, and 38 years. The childhood personal-history characteristics studied were known predictors of age-related disease and mortality, and were measured prospectively during childhood. Personal-history characteristics of familial longevity, childhood social class, adverse childhood experiences, and childhood health, intelligence, and self-control all predicted differences in cohort members’ adulthood Pace of Aging. Accumulation of more personal-history risks predicted faster Pace of Aging. Because trials of anti-aging therapies will need to ascertain personal histories retrospectively, we replicated results using cohort members’ retrospective personal-history reports made in adulthood. Because many trials recruit participants from clinical settings, we replicated results in the cohort subset who had recent health system contact according to electronic medical records. Quick, inexpensive measures of trial participants’ early personal histories can enable clinical trials to study who volunteers for trials, who adheres to treatment, and who responds to anti-aging therapies.
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Childhood body mass index and endothelial dysfunction evaluated by peripheral arterial tonometry in early midlife | 2017
Williams, M. J. A., Milne, B. J., Ambler, ... Show all » A., Theodore, R., Ramrakha, S., Caspi, A., Moffitt, T. E., Poulton, R. « Hide
International Journal of Obesity, 2017, 41(9), 1355-1360.
DOI: 10.1038/ijo.2017.108
Link to full publication »
Our ref: RO698
Show abstract » BACKGROUND/OBJECTIVES: Endothelial dysfunction predicts mortality but it is unknown whether childhood obesity predicts adult endothelial dysfunction. The aim of this study was to determine whether anthropometric indices of body fat in childhood, adolescence and early midlife are associated with endothelial dysfunction in early midlife. SUBJECTS/METHODS: Participants belonged to a representative birth cohort of 1037 individuals born in Dunedin, New Zealand in 1972 and 1973 and followed to age 38 years, with 95% retention (the Dunedin Multidisciplinary Health and Development Study). We assessed anthropometric indices of obesity at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32 and 38 years. We tested associations between endothelial function assessed by peripheral arterial tonometry (PAT) at age 38 and; age 38 cardiovascular risk factors; age 3 body mass index (BMI); and four BMI trajectory groups from childhood to early midlife. RESULTS: Early midlife endothelial dysfunction was associated with BMI, large waist circumference, low high-density lipoprotein cholesterol, low cardiorespiratory fitness and increased high-sensitivity C-reactive protein. After adjustment for sex and childhood socioeconomic status, 3-year-olds with BMI 1 s.d. above the mean had Framingham-reactive hyperemia index (F-RHI) ratios that were 0.10 below those with normal BMI (beta=-0.10, 95% confidence interval (CI) -0.17 to -0.03, P=0.007) at age 38. Cohort members in the 'overweight', 'obese' and 'morbidly obese' trajectories had F-RHI ratios that were 0.08 (beta=-0.08, 95% CI -0.14 to -0.03, P=0.003), 0.13 (beta=-0.13, 95% CI -0.21 to -0.06, P<0.001) and 0.17 (beta=-0.17, 95% CI -0.33 to -0.01, P=0.033), respectively, below age-peers in the 'normal' trajectory. CONCLUSIONS: Childhood BMI and the trajectories of BMI from childhood to early midlife predict endothelial dysfunction evaluated by PAT in early midlife.
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The Origins of Cognitive Deficits in Victimized Children: Implications for Neuroscientists and Clinicians | 2017
Danese, A., Moffitt, T. E., Arseneault, ... Show all » L., Bleiberg, B. A., Dinardo, P. B., Gandelman, S. B., Houts, R., Ambler, A., Fisher, H. L., Poulton, R., Caspi, A. « Hide
Am J Psychiatry, 2017, 174(4), 349-361.
DOI: 10.1176/appi.ajp.2016.16030333
Our ref: RO697
Show abstract » OBJECTIVE: Individuals reporting a history of childhood violence victimization have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. The authors used data from two large cohort studies to address these research questions directly. METHOD: The authors tested the association between prospectively collected measures of childhood violence victimization and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the U.K. E-Risk Study and 1,037 members of the New Zealand Dunedin Study who were followed up from birth until ages 18 and 38 years, respectively. Multiple measures of victimization and cognition were used, and comparisons were made of cognitive scores for twins discordant for victimization. RESULTS: Individuals exposed to childhood victimization had pervasive impairments in clinically relevant cognitive functions, including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimized individuals were largely explained by cognitive deficits that predated childhood victimization and by confounding genetic and environmental risks. CONCLUSIONS: Findings from two population-representative birth cohorts totaling more than 3,000 individuals and born 20 years and 20,000 km apart suggest that the association between childhood violence victimization and later cognition is largely noncausal, in contrast to conventional interpretations. These findings support the adoption of a more circumspect approach to causal inference in the neuroscience of stress. Clinically, cognitive deficits should be conceptualized as individual risk factors for victimization as well as potential complicating features during treatment.
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Association of Childhood Blood Lead Levels With Cognitive Function and Socioeconomic Status at Age 38 Years and With IQ Change and Socioeconomic Mobility Between Childhood and Adulthood | 2017
Reuben, A., Caspi, A., Belsky, ... Show all » D. W., Broadbent, J., Harrington, H., Sugden, K., Houts, R. M., Ramrakha, S., Poulton, R., Moffitt, T. E. « Hide
JAMA, 2017, 317(12), 1244-1251.
DOI: 10.1001/jama.2017.1712
Our ref: RO696
Show abstract » mportance: Many children in the United States and around the world are exposed to lead, a developmental neurotoxin. The long-term cognitive and socioeconomic consequences of lead exposure are uncertain. Objective: To test the hypothesis that childhood lead exposure is associated with cognitive function and socioeconomic status in adulthood and with changes in IQ and socioeconomic mobility between childhood and midlife. Design, Setting, and Participants: A prospective cohort study based on a population-representative 1972-1973 birth cohort from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (until December 2012). Exposures: Childhood lead exposure ascertained as blood lead levels measured at age 11 years. High blood lead levels were observed among children from all socioeconomic status levels in this cohort. Main Outcomes and Measures: The IQ (primary outcome) and indexes of Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed (secondary outcomes) were assessed at age 38 years using the Wechsler Adult Intelligence Scale-IV (WAIS-IV; IQ range, 40-160). Socioeconomic status (primary outcome) was assessed at age 38 years using the New Zealand Socioeconomic Index-2006 (NZSEI-06; range, 10 [lowest]-90 [highest]). Results: Of 1037 original participants, 1007 were alive at age 38 years, of whom 565 (56%) had been lead tested at age 11 years (54% male; 93% white). Mean (SD) blood lead level at age 11 years was 10.99 (4.63) microg/dL. Among blood-tested participants included at age 38 years, mean WAIS-IV score was 101.16 (14.82) and mean NZSEI-06 score was 49.75 (17.12). After adjusting for maternal IQ, childhood IQ, and childhood socioeconomic status, each 5-microg/dL higher level of blood lead in childhood was associated with a 1.61-point lower score (95% CI, -2.48 to -0.74) in adult IQ, a 2.07-point lower score (95% CI, -3.14 to -1.01) in perceptual reasoning, and a 1.26-point lower score (95% CI, -2.38 to -0.14) in working memory. Associations of childhood blood lead level with deficits in verbal comprehension and processing speed were not statistically significant. After adjusting for confounders, each 5-microg/dL higher level of blood lead in childhood was associated with a 1.79-unit lower score (95% CI, -3.17 to -0.40) in socioeconomic status. An association between greater blood lead levels and a decline in IQ and socioeconomic status from childhood to adulthood was observed with 40% of the association with downward mobility mediated by cognitive decline from childhood. Conclusions and Relevance: In this cohort born in New Zealand in 1972-1973, childhood lead exposure was associated with lower cognitive function and socioeconomic status at age 38 years and with declines in IQ and with downward social mobility. Childhood lead exposure may have long-term ramifications.
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The Longitudinal Study of Aging in Human Young Adults: Knowledge Gaps and Research Agenda | 2017
Moffitt, T. E., Belsky, D. W., Danese, ... Show all » A., Poulton, R., Caspi, A. « Hide
J Gerontol A Biol Sci Med Sci, 2017, 72(2), 210-215.
DOI: 10.1093/gerona/glw191
Our ref: RO695
Show abstract » To prevent onset of age-related diseases and physical and cognitive decline, interventions to slow human aging and extend health span must eventually be applied to people while they are still young and healthy. Yet most human aging research examines older adults, many with chronic disease, and little is known about aging in healthy young humans. METHOD: This article explains how this knowledge gap is a barrier to extending health span and puts forward the case that geroscience should invest in researching the pace of aging in young adults. As one illustrative example, we describe an initial effort to study the pace of aging in a young-adult birth cohort by using repeated waves of biomarkers collected across the third and fourth decades to quantify the pace of coordinated physiological deterioration across multiple organ systems (eg, pulmonary, periodontal, cardiovascular, renal, hepatic, metabolic, and immune function). RESULTS: Findings provided proof of principle that it is possible to quantify individual variation in the pace of aging in young adults still free of age-related diseases. CONCLUSIONS: This article articulates research needs to improve longitudinal measurement of the pace of aging in young people, to pinpoint factors that slow or speed the pace of aging, to compare pace of aging against genomic clocks, to explain slow-aging young adults, and to apply pace of aging in preventive clinical trials of antiaging therapies. This article puts forward a research agenda to fill the knowledge gap concerning lifelong causes of aging.
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Enduring mental health: Prevalence and prediction | 2017
Schaefer, J. D., Caspi, A., Belsky, ... Show all » D. W., Harrington, H., Houts, R., Horwood, L, J., Hussong, A., Ramrakha, S., Poulton, R., Moffitt, T. E. « Hide
J Abnorm Psychol, 2017, 126(2), 212-224.
DOI: 10.1037/abn0000232
download pdf Our ref: RO694
Show abstract » We review epidemiological evidence indicating that most people will develop a diagnosable mental disorder, suggesting that only a minority experience enduring mental health. This minority has received little empirical study, leaving the prevalence and predictors of enduring mental health unknown. We turn to the population-representative Dunedin cohort, followed from birth to midlife, to compare people never-diagnosed with mental disorder (N = 171; 17% prevalence) to those diagnosed at 1-2 study waves, the cohort mode (N = 409). Surprisingly, compared to this modal group, never-diagnosed Study members were not born into unusually well-to-do families, nor did their enduring mental health follow markedly sound physical health, or unusually high intelligence. Instead, they tended to have an advantageous temperament/personality style, and negligible family history of mental disorder. As adults, they report superior educational and occupational attainment, greater life satisfaction, and higher-quality relationships. Our findings draw attention to "enduring mental health" as a revealing psychological phenotype and suggest it deserves further study. (PsycINFO Database Record
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Periodontitis is not associated with metabolic risk during the fourth decade of life | 2017
Shearer, D, M., Thomson, W. M., ... Show all » Broadbent, J, M., Mann, J., Poulton, R. « Hide
Journal of Clinical Periodontology, 2017, 44(1), 22-30.
DOI: 10.1111/jcpe.12641
Our ref: RO693
Show abstract » Aim: To examine associations between periodontitis and developmental trajectories of glycated haemoglobin (HbA1c) during the third and fourth decades in an initially healthy sample. Materials and methods: HbA1c data collected at ages 26, 32 and 38 in the prospective Dunedin Multidisciplinary Health and Development Study were used to assign study members (n = 893) to trajectories applying group-based trajectory modelling (GBTM). The model allowed the statistical linking of baseline demographic, smoking and waist-height ratio covariates to group membership probability; and added a time-varying covariate (periodontitis) to the trajectories themselves to examine whether events that occurred during the course of the trajectory altered its course. Results: Three HbA1c trajectory groups were identified: “Low” (n = 98, 11.0%); “Medium” (n = 482, 54.0%); and “High” (n = 313, 35.0%) with mean HbA1c of 29.6, 34.1 and 38.7 mmol/mol, respectively, at age 38. Having periodontitis at 32 and 38 was associated with an upward shift in the trajectories. However, none of the associations were statistically significant. Conclusions: Periodontitis was not found to be associated with dysglycaemia over 12 years from early adulthood into early middle age. This suggests that any influence periodontitis may have on dysglycaemia develops later in life.
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Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health | 2016
Reuben, A., Moffitt, T. E., Caspi, ... Show all » A., Belsky, D. W., Harrington, H., Hogan, S., Schroeder, F., Hogan, S., Ramrakha, S., Poulton, R. « Hide
Journal of Child Psychology and Psychiatry, 2016, 57(10), 1103-1112.
DOI: 10.1111/jcpp.12621
download pdf Our ref: RO692
Show abstract » Background: Adverse childhood experiences (ACEs; e.g. abuse, neglect, and parental loss) have been associated with increased risk for later-life disease and dysfunction using adults’ retrospective self-reports of ACEs. Research should test whether associations between ACEs and health outcomes are the same for prospective and retrospective ACE measures. Methods: We estimated agreement between ACEs prospectively recorded throughout childhood (by Study staff at Study member ages 3, 5, 7, 9, 11, 13, and 15) and retrospectively recalled in adulthood (by Study members when they reached age 38), in the population-representative Dunedin cohort (N = 1,037). We related both retrospective and prospective ACE measures to physical, mental, cognitive, and social health at midlife measured through both objective (e.g. biomarkers and neuropsychological tests) and subjective (e.g. self-reported) means. Results: Dunedin and U.S. Centers for Disease Control ACE distributions were similar. Retrospective and prospective measures of adversity showed moderate agreement (r = .47, p < .001; weighted Kappa = .31, 95% CI: .27–.35). Both associated with all midlife outcomes. As compared to prospective ACEs, retrospective ACEs showed stronger associations with life outcomes that were subjectively assessed, and weaker associations with life outcomes that were objectively assessed. Recalled ACEs and poor subjective outcomes were correlated regardless of whether prospectively recorded ACEs were evident. Individuals who recalled more ACEs than had been prospectively recorded were more neurotic than average, and individuals who recalled fewer ACEs than recorded were more agreeable. Conclusions: Prospective ACE records confirm associations between childhood adversity and negative life outcomes found previously using retrospective ACE reports. However, more agreeable and neurotic dispositions may, respectively, bias retrospective ACE measures toward underestimating the impact of adversity on objectively measured life outcomes and overestimating the impact of adversity on self-reported outcomes. Associations between personality factors and the propensity to recall adversity were extremely modest and warrant further investigation. Risk predictions based on retrospective ACE reports should utilize objective outcome measures. Where objective outcome measurements are difficult to obtain, correction factors may be warranted.
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Childhood forecasting of a small segment of the population with large economic burden. | 2016
Caspi, A., Houts, R. M., Belsky, ... Show all » D. W., Harrington, H., Hogan, S., Ramrakha, S., Poulton, R., Moffitt, T. E. « Hide
Nature Human Behaviour, 2016, 1(005), .
doi:10.1038/s41562-016-0005
Our ref: RO691
Show abstract » Policymakers are interested in early-years interventions to ameliorate childhood risks. They hope for improved adult outcomes in the long run that bring a return on investment. The size of the return that can be expected partly depends on how strongly childhood risks forecast adult outcomes, but there is disagreement about whether childhood determines adulthood. We integrated multiple nationwide administrative databases and electronic medical records with the four-decade-long Dunedin birth cohort study to test child-to-adult prediction in a different way, using a population-segmentation approach. A segment comprising 22% of the cohort accounted for 36% of the cohort’s injury insurance claims; 40% of excess obese kilograms; 54% of cigarettes smoked; 57% of hospital nights; 66% of welfare benefits; 77% of fatherless child-rearing; 78% of prescription fills; and 81% of criminal convictions. Childhood risks, including poor brain health at three years of age, predicted this segment with large effect sizes. Early-years interventions that are effective for this population segment could yield very large returns on investment.

Full text of this article: http://rdcu.be/nMf9

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The dynamic, complex and diverse living and care arrangements of young New Zealanders: implications for policy | 2016
Sligo, J., McAnally, H.M., Tansley, ... Show all » J.E., Baxter, J., Bolton, A.E., Skillander, K.M., Hancox, R. J. « Hide
Kotuitui: New Zealand Journal of Social Sciences Online, 2016, DOI: 10.1080/1177083X.2016.1196715.
DOI: 10.1080/1177083X.2016.1196715
Our ref: NZ94
Show abstract » The living arrangements of young people in New Zealand are diverse and often complex. In this article we report the range of care and living arrangements of 209 15-year-old New Zealanders, 47 of whom identified as Maori. These young people were participants in the second generation of a cohort study. Data were collected from their parents via a life history calendar and analysed for variety and consistency of care arrangements, household membership and transitions. Few participants had a consistent pattern of parental care arrangements and most had experienced multiple changes in household composition and frequent changes of address. We conclude that the whanau/family lives of many young New Zealanders are complex and dynamic. These observations contrast with the conventional notions of family life that form the basis for New Zealand’s family policies. We argue that social policies and services impacting on young people need to reflect the lived reality of young people if they are to meet young people’s needs.
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The Longitudinal Study of Aging in Human Young Adults: Knowledge Gaps and Research Agenda | 2016
Moffitt, Terrie E., Belsky, Daniel W., Danese, ... Show all » Andrea, Poulton, Richie, Caspi, Avshalom « Hide
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2016, first published online October 7, 2016 doi:10.1093/gerona/glw191 .
http://biomedgerontology.oxfordjournals.org/content/early/2016/10/07/gerona.glw191.abstract
Our ref: RO690
Show abstract » Background: To prevent onset of age-related diseases and physical and cognitive decline, interventions to slow human aging and extend health span must eventually be applied to people while they are still young and healthy. Yet most human aging research examines older adults, many with chronic disease, and little is known about aging in healthy young humans.Method: This article explains how this knowledge gap is a barrier to extending health span and puts forward the case that geroscience should invest in researching the pace of aging in young adults. As one illustrative example, we describe an initial effort to study the pace of aging in a young-adult birth cohort by using repeated waves of biomarkers collected across the third and fourth decades to quantify the pace of coordinated physiological deterioration across multiple organ systems (eg, pulmonary, periodontal, cardiovascular, renal, hepatic, metabolic, and immune function).Results: Findings provided proof of principle that it is possible to quantify individual variation in the pace of aging in young adults still free of age-related diseases.Conclusions: This article articulates research needs to improve longitudinal measurement of the pace of aging in young people, to pinpoint factors that slow or speed the pace of aging, to compare pace of aging against genomic clocks, to explain slow-aging young adults, and to apply pace of aging in preventive clinical trials of antiaging therapies. This article puts forward a research agenda to fill the knowledge gap concerning lifelong causes of aging.
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High risk glycated hemoglobin trajectories established by mid-20s: findings from a birth cohort study | 2016
Shearer, D.M., Thomson, W. M., Broadbent, ... Show all » J. M. , McLean, R., Poulton, R., Mann, J. « Hide
BMJ Open Diabetes Research and Care, 2016, 4(e000243), doi:10.1136/bmjdrc-2016-000243.
http://drc.bmj.com/content/4/1/e000243
Our ref: RO689
Show abstract » Objective To describe the natural history of glycemia (as measured by glycated hemoglobin (HbA1c)) over 12 years using group-based trajectory modeling (GBTM), and to examine baseline predictors of trajectory. Research design and methods HbA1c data collected at ages 26, 32 and 38 in the long-running, prospective Dunedin Multidisciplinary Health and Development Study were used to assign study members (n=893) to trajectories applying GBTM. A generalization of the model allowed the statistical linking of baseline demographic, smoking and anthropometric characteristics to group membership probability. Results Mean HbA1c increased with age, as did prevalence of prediabetes, diabetes and dysglycemia. The greatest increase occurred between ages 26 and 32. Glycemic health status at age 26 predicted glycemic health status at age 38. 3 HbA1c trajectory groups were identified: ‘low’ (n=98, 11.0%); ‘medium’ (n=482, 54.0%); and ‘high’ (n=313, 35.0%) with mean HbA1c of 29.6, 34.1, and 38.7 mmol/mol, respectively, at age 38. High waist circumference (=880 mm for women and =1020 mm for men), high waist-height ratio (=0.50), and being a smoker at age 26 predicted membership of the least favorable trajectory over the next 12 years. High body mass index (=30) at age 26 did not predict of trajectory. Conclusions Trajectories of HbA1c are established relatively early in adulthood. HbA1c levels, waist circumference, waist-height ratio, and smoking status at age 26 are valid clinical predictors for future dysglycemic risk. The identification of HbA1c trajectories and their predictors introduces the possibility of an individualized approach to prevention at an earlier stage than is currently done.
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Which adolescents develop persistent substance dependence in adulthood? Using population-representative longitudinal data to inform universal risk assessment | 2016
Meier, M.H., Hall, W., Caspi, ... Show all » A., Belsky, D.W., Cerda, M., Harrington, H. L., Houts, R., Poulton, R. , Moffitt, T. E. « Hide
Psychological Medicine, 2016, 46(4), 877-889.
doi.org/10.1017/S0033291715002482
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Our ref: RO688
Show abstract » Importance: Longitudinal studies have shown that youth exposed to particular risks are more likely to develop substance dependence, and these studies point to potential targets for prevention. They do not, however, directly address the pressing public health question of how accurately we can predict the development of persistent substance dependence in the general population. Objective: To determine how accurately childhood and adolescent risk factors can predict persistent substance dependence. Design: A 38-year, prospective, longitudinal study of a representative birth cohort. Setting: The Dunedin Multidisciplinary Health and Development Study of New Zealand. Participants: The study included 1,037 male and female participants. Exposure: Prospectively assessed predictors included family history of substance dependence, childhood psychopathology (conduct disorder, depression), early exposure to substances, frequent substance use in adolescence, sex, and childhood socioeconomic status. Main Outcome Measures: Persistent substance dependence was defined as dependence on one or more of alcohol, tobacco, cannabis, or hard-drugs at three or more assessment ages: ages 21, 26, 32, and 38. Results: An ROC curve analysis showed that a cumulative index of childhood and adolescent risk predicted persistent adult substance dependence with an AUC (area-under-the-curve) of 0.80 a large effect. Daily tobacco use in adolescence was the single best predictor of later persistent substance dependence, accurately identifying 68% of those who developed persistent substance dependence in adulthood. Nearly 1 in 2 adolescents who used tobacco on a daily basis developed severe substance dependence that persisted through early midlife. Conclusions and Relevance: We can predict with considerable accuracy which individuals will develop persistent substance dependence in adulthood based on information obtained in childhood and adolescence. By ascertaining adolescent tobacco use, clinicians, parents, and teachers, can efficiently identify the majority of individuals who will struggle with persistent substance dependence in adulthood.
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Thumb-sucking, nail-biting and atopic sensitisation, asthma, and hay fever | 2016
Lynch, S.J., Sears, M.R., Hancox, ... Show all » R. J. « Hide
Pediatrics, 2016, 138(2), e20160443; DOI: 10.1542/peds.2016-0443.
http://pediatrics.aappublications.org/content/138/2/e20160443
Our ref: RO687
Show abstract » Background: The hygiene hypothesis suggests that early-life exposure to microbial organisms reduces the risk of developing allergies. Thumb-sucking and nail-biting are common childhood habits that may increase microbial exposures. We tested the hypothesis that children who suck their thumbs or bite their nails have a lower risk of developing atopy, asthma, and hay fever in a population-based birth-cohort followed to adulthood. Methods: Parents reported children’s thumb-sucking and nail-biting habits when their children were ages 5, 7, 9, and 11 years. Atopic sensitisation was defined as a positive skin prick test (>2mm weal) to at least one common allergen at 13 and 32 years. Associations between thumb-sucking and nail-biting in childhood, and atopic sensitisation, asthma, and hay fever at these ages were assessed using logistic regression with adjustments for sex and other potential confounding factors: parental atopy, breastfeeding, pet ownership, household crowding, socio-economic status, and parental smoking. Results: 31% of children were frequent thumb-suckers or nail-biters at at least one age. These children had a lower risk of atopic sensitisation at age 13 years (OR=0.67 [95%CI: 0.48, 0.92], p=0.013) and age 32 years (OR=0.61 [95%CI: 0.46, 0.81], p=0.001). These associations persisted when adjusted for multiple confounding factors. Children who had both habits had a lower risk of atopic sensitisation than those who only had one. No associations were found for nail-biting, thumb-sucking and asthma or hay fever at either age. Conclusion: Children who suck their thumbs or bite their nails are less likely to have atopic sensitisation in childhood and adulthood.
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The relationship between body fat and respiratory function in young adults | 2016
Sutherland, T.J.T., McLachlan, C. R. , Sears, ... Show all » M.R., Poulton, R., Hancox, R. J. « Hide
European Respiratory Journal, 2016, 48(3), 734-747.
http://erj.ersjournals.com/content/48/3/734
Our ref: RO686
Show abstract » The relationship between adiposity and respiratory function is poorly understood. Most studies investigating this have used indirect measures of body fat and few have assessed how changes in adiposity influence lung function. Body fat measured by bio-electrical impedance analysis, body mass index, waist circumference, spirometry, body plethysmography and transfer factor were measured at ages 32 and 38 years in 361 non-smoking, non-asthmatic participants from a population-based birth cohort. Higher percentage body fat was associated with lower spirometric and plethysmographic lung volumes, but not with airflow obstruction, or transfer factor at 32 years. Changes in adiposity between ages 32 and 38 years were inversely associated with changes in lung volumes. These associations were generally stronger in men than women, but an association between increasing adiposity and lower airway function (forced expiratory volume in 1 s/forced vital capacity) was only found in women. Similar associations were found for body mass index and waist circumference. Higher percentage body fat is associated with lower lung volumes. Direct and indirect measures of adiposity had similar associations with lung function. Adiposity had a greater effect on lung volumes in men than women but was associated with airway function only in women. There was little evidence that adiposity influenced transfer factor.
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Persistent cannabis dependence and alcohol dependence represent risks for midlife economic and social problems: A longitudinal cohort study | 2016
Cerda, M., Moffitt, T.E., Meier, ... Show all » M.H., /Harrington, H. L., Houts, R., Ramrakha, S., Hogan, S., Poulton, R., Caspi, A. « Hide
Clinical Psychological Science, 2016, Published online before print 22 March 2016, DOI: 10.1177/2167702616630958.
DOI: 10.1177/2167702616630958
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Our ref: RO685
Show abstract » With the increasing legalization of cannabis, understanding the consequences of cannabis use is particularly timely. We examined the association between cannabis use and dependence, prospectively assessed between ages 18 and 38, and economic and social problems at age 38. We studied participants in the Dunedin Longitudinal Study, a cohort (N = 1,037) followed from birth to age 38. Study members with regular cannabis use and persistent dependence experienced downward socioeconomic mobility, more financial difficulties, workplace problems, and relationship conflict in early midlife. Cannabis dependence was not linked to traffic-related convictions. Associations were not explained by socioeconomic adversity, childhood psychopathology, achievement orientation, or family structure; cannabis-related criminal convictions; early onset of cannabis dependence; or comorbid substance dependence. Cannabis dependence was associated with more financial difficulties than was alcohol dependence; no difference was found in risks for other economic or social problems. Cannabis dependence is not associated with fewer harmful economic and social problems than alcohol dependence.
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Systemic inflammation and lung function: A longitudinal analysis | 2016
Hancox, R. J., Gray, A.R., Sears, ... Show all » M.R., Poulton, R. « Hide
Respiratory Medicine, 2016, 111 54-59.
http://www.resmedjournal.com/article/S0954-6111(15)30098-6/abstract
Our ref: RO684
Show abstract » Abstract: Background. Systemic inflammation is associated with impaired lung function in healthy adults as well as in patients with lung disease. The mechanism for this association is unknown and it is unclear if systemic inflammation leads to impaired lung function or if poor lung function leads to inflammation. We explored the temporal associations between blood C-reactive protein (CRP), fibrinogen, and white blood cells, and lung function in young adults. Methods. Spirometry, plethysmography, and diffusion capacity were measured in a population-based cohort at ages 32 and 38 years. Highsensitivity CRP, fibrinogen, and white blood cells were measured at the same ages. Results. Higher levels of CRP and, to a lesser extent, fibrinogen were associated with lower lung volumes in cross-sectional analyses at both ages 32 and 38 years. Higher CRP and fibrinogen at age 32 were associated with higher FEV1 and FEV1/FVC at age 38, but not other measures of lung function. Lower lung volumes (total lung capacity, functional residual capacity, and residual volume) but not airflow obstruction (FEV1/FVC) at age 32 were associated with higher CRP at age 38. Associations between age 32 lung function and fibrinogen at follow-up were weaker, but consistent. There were no longitudinal associations between white blood cells and lung function. Conclusions. We found no evidence that systemic inflammation causes a decline in lung function. However, lower lung volumes were associated with higher CRP and fibrinogen at follow-up indicating that pulmonary restriction may be a risk factor for systemic inflammation. The mechanism for this association remains unclear.
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Associations between cannabis use and physical health problems in early midlife: a longitudinal comparison of persistent cannabis versus tobacco users | 2016
Meier, M.H., Caspi, A., Cerda, ... Show all » M., Hancox, R. J., Harrington, H. L., Houts, R., Poulton, R., Ramrakha, S., Thomson, W. M., Moffitt, T.E. « Hide
JAMA Psychiatry, 2016, .
doi:10.1001/jamapsychiatry.2016.0637
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Our ref: RO683
Show abstract » Importance: After major policy changes in the United States, policymakers, health care professionals, and the general public seek information about whether recreational cannabis use is associated with physical health problems later in life. Objective: To test associations between cannabis use over 20 years and a variety of physical health indexes at early midlife.
Design, Setting, and Participants: Participants belonged to a representative birth cohort of 1037 individuals born in Dunedin, New Zealand, in 1972 and 1973 and followed to age 38 years, with 95% retention (the Dunedin Multidisciplinary Health and Development Study). We tested whether cannabis use from ages 18 to 38 years was associated with physical health at age 38, even after controlling for tobacco use, childhood health, and childhood socioeconomic status. We also tested whether cannabis use from ages 26 to 38 years was associated with within-individual health decline using the same measures of health at both ages. Exposures: We assessed frequency of cannabis use and cannabis dependence at ages 18, 21, 26, 32, and 38 years. Main Outcomes and Measures: We obtained laboratory measures of physical health (periodontal health, lung function, systemic inflammation, and metabolic health), as well as self-reported physical health, at ages 26 and 38 years. Results: The 1037 study participants were 51.6% male (n = 535). Of these, 484 had ever used tobacco daily and 675 had ever used cannabis. Cannabis use was associated with poorer periodontal health at age 38 years and within-individual decline in periodontal health from ages 26 to 38 years. For example, cannabis joint-years from ages 18 to 38 years was associated with poorer periodontal health at age 38 years, even after controlling for tobacco pack-years (ß = 0.12; 95% CI, 0.05-0.18; P <.001). Additionally, cannabis joint-years from ages 26 to 38 years was associated with poorer periodontal health at age 38 years, even after accounting for periodontal health at age 26 years and tobacco pack-years (ß = 0.10; 95% CI, 0.05-0.16; P <.001) However, cannabis use was unrelated to other physical health problems. Unlike cannabis use, tobacco use was associated with worse lung function, systemic inflammation, and metabolic health at age 38 years, as well as within-individual decline in health from ages 26 to 38 years. Conclusions and Relevance: Cannabis use for up to 20 years is associated with periodontal disease but is not associated with other physical health problems in early midlife.

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The Genetics of Success: How single nucleotide polymorphisms associated with educational attainment relate to life-course development | 2016
Belsky, D.W., Moffitt, T.E., Corcoran, ... Show all » D.L., Domingue, B., Harrington, H. L., Houts, R., Ramrakha, S., Sugden, K., Williams, B.S., Poulton, R., Caspi, A. « Hide
Psychological Science, 2016, .
doi:10.1177/0956797616643070
download pdf Our ref: RO682
Show abstract » A previous genome-wide association study (GWAS) of more than 100,000 individuals identified molecular-genetic predictors of educational attainment. We undertook in-depth life-course investigation of the polygenic score derived from this GWAS using the four-decade Dunedin Study (N = 918). There were five main findings. First, polygenic scores predicted adult economic outcomes even after accounting for educational attainments. Second, genes and environments were correlated: Children with higher polygenic scores were born into better-off homes. Third, children’s polygenic scores predicted their adult outcomes even when analyses accounted for their social-class origins; social-mobility analysis showed that children with higher polygenic scores were more upwardly mobile than children with lower scores. Fourth, polygenic scores predicted behavior across the life course, from early acquisition of speech and reading skills through geographic mobility and mate choice and on to financial planning for retirement. Fifth, polygenic-score associations were mediated by psychological characteristics, including intelligence, self-control, and interpersonal skill. Effect sizes were small. Factors connecting DNA sequence with life outcomes may provide targets for interventions to promote population-wide positive development.
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Telomere length and periodontal attachment loss: a prospective cohort study | 2016
Thomson, W. M., Zeng, J., Broadbent, ... Show all » J. M. , Foster-Page, L.A. , Shalev, I., Moffitt, T.E., Caspi, A., Williams, S.M., Braithwaite, A., Robertson, S. P. , Poulton, R. « Hide
Journal of Clinical Periodontology, 2016, 43(2), 121-127.
http://onlinelibrary.wiley.com/doi/10.1111/jcpe.12499/full
Our ref: RO680
Show abstract » Aim: To examine the association between telomere erosion and periodontitis in a longstanding prospective cohort study of New Zealand adults. Specific hypotheses tested were: (1) that exposure to periodontitis at ages 26 and 38 was associated with accelerated leucocyte telomere erosion; and (2) that accelerated leucocyte telomere erosion was associated with higher rates of periodontitis by ages 26 and 38. Materials and Methods: Periodontal attachment loss data were collected at ages 26 and 38. Blood samples taken at the same ages were analysed to obtain estimates of leucocyte telomere length and erosion over a 12-year period. Results: Overall, mean telomere length reduced by 0.15 TS ratio (adjusted) from age 26 to 38 among the 661 participants reported on here. During the same period, the mean attachment loss increased by 10%, after adjusting for sex, socio-economic status and smoking. Regression models showed that attachment loss did not predict telomere length, and that telomere erosion did not predict attachment loss. Conclusions: Although both periodontitis and telomere length are age-dependent, they do not appear to be linked, suggesting that determination of leucocyte telomere length may not be a promising clinical approach for identifying people who are at risk for periodontitis.
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