Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes | 2025
van der Laan, Camiel M. Ip, Hill F. Schipper, Marijn Hottenga, Jouke-Jan St Pourcain, ... Show all » Beate Zayats, Tetyana Pool, René Krapohl, Eva M. L. Brikell, Isabell Soler Artigas, María Cabana-Domínguez, Judit Llonga, Natalia Nolte, Ilja M. Bolhuis, Koen Palviainen, Teemu Zafarmand, Hadi Gordon, Scott Aliev, Fazil Burt, S. Alexandra Wang, Carol A. Saunders, Gretchen Karhunen, Ville Adkins, Daniel E. Border, Richard Peterson, Roseann E. Prinz, Joseph A. Thiering, Elisabeth Vilor-Tejedor, Natàlia Ahluwalia, Tarunveer S. Allegrini, Andrea Rimfeld, Kaili Chen, Qi Lu, Yi Martin, Joanna Bosch, Rosa Ramos-Quiroga, Josep Antoni Neumann, Alexander Ensink, Judith Grasby, Katrina L. Morosoli, José J. Tong, Xiaoran Marrington, Shelby Scott, James G. Shabalin, Andrey A. Corley, Robin Evans, Luke M. Sugden, Karen Alemany, Silvia Sass, Lærke Vinding, Rebecca Ehli, Erik A. Hagenbeek, Fiona A. Derks, Eske M. Larsson, Henrik Snieder, Harold Cecil, Charlotte Whipp, Alyce M. Korhonen, Tellervo Vuoksimaa, Eero Rose, Richard J. Uitterlinden, André G. 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 A. Smolen, Andrew Stallings, Michael Wadsworth, Sally Wall, Tamara L. Eaves, Lindon Silberg, Judy L. Miller, Allison Havdahl, Alexandra Llop, Sabrina Lopez-Espinosa, Maria-Jose Bønnelykke, Klaus Sunyer, Jordi Arseneault, Louise Standl, Marie Heinrich, Joachim Boden, Joseph Pearson, John Horwood, John Kennedy, Martin Poulton, Richie Maes, Hermine H. Hewitt, John Copeland, William E. Middeldorp, Christel M. Williams, Gail M. Wray, Naomi Järvelin, Marjo-Riitta McGue, Matt Iacono, William Caspi, Avshalom Moffitt, Terrie E. Whitehouse, Andrew J. O. Pennell, Craig E. Klump, Kelly L. Jiang, Chang 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
Nature Genetics, 2025, .
10.1038/s41588-025-02295-y
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Our ref: RO832
Show abstract » We performed a genome-wide association meta-analysis (GWAMA) of 290,134 attention-deficit/hyperactivity disorder (ADHD) symptom measures of 70,953 unique individuals from multiple raters, ages and instruments (ADHDSYMP). Next, we meta-analyzed the results with a study of ADHD diagnosis (ADHDOVERALL). ADHDSYMP returned no genome-wide significant variants. We show that the combined ADHDOVERALL GWAMA identified 39 independent loci, of which 17 were new. Using a recently developed gene-mapping method, Fine-mapped Locus Assessment Model of Effector genes, we identified 22 potential ADHD effector genes implicating several new biological processes and pathways. Moderate negative genetic correlations (rg < −0.40) were observed with multiple cognitive traits. In three cohorts, polygenic scores (PGSs) based on ADHDOVERALL outperformed PGSs based on ADHD symptoms and diagnosis alone. Our findings support the notion that clinical ADHD is at the extreme end of a continuous liability that is indexed by ADHD symptoms. We show that including ADHD symptom counts helps to identify new genes implicated in ADHD.
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