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Nat Genet DOI:10.1038/s41588-018-0269-7

Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.

Publication TypeJournal Article
Year of Publication2019
AuthorsDemontis, D, Walters, RK, Martin, J, Mattheisen, M, Als, TD, Agerbo, E, Baldursson, G, Belliveau, R, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Cerrato, F, Chambert, K, Churchhouse, C, Dumont, A, Eriksson, N, Gandal, M, Goldstein, JI, Grasby, KL, Grove, J, Gudmundsson, OO, Hansen, CS, Hauberg, MEngel, Hollegaard, MV, Howrigan, DP, Huang, H, Maller, JB, Martin, AR, Martin, NG, Moran, J, Pallesen, J, Palmer, DS, Pedersen, CBøcker, Pedersen, MGiørtz, Poterba, T, Poulsen, JBuchhave, Ripke, S, Robinson, EB, F Satterstrom, K, Stefansson, H, Stevens, C, Turley, P, G Walters, B, Won, H, Wright, MJ, Andreassen, OA, Asherson, P, Burton, CL, Boomsma, DI, Cormand, B, Dalsgaard, S, Franke, B, Gelernter, J, Geschwind, D, Hakonarson, H, Haavik, J, Kranzler, HR, Kuntsi, J, Langley, K, Lesch, K-P, Middeldorp, C, Reif, A, Rohde, LAugusto, Roussos, P, Schachar, R, Sklar, P, Sonuga-Barke, EJS, Sullivan, PF, Thapar, A, Tung, JY, Waldman, ID, Medland, SE, Stefansson, K, Nordentoft, M, Hougaard, DM, Werge, T, Mors, O, Mortensen, PBo, Daly, MJ, Faraone, SV, Børglum, AD, Neale, BM
Corporate AuthorsADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team
JournalNat Genet
Volume51
Issue1
Pages63-75
Date Published2019 Jan
ISSN1546-1718
KeywordsAdolescent, Attention Deficit Disorder with Hyperactivity, Brain, Child, Child, Preschool, Cohort Studies, Female, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Risk
Abstract

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

DOI10.1038/s41588-018-0269-7
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/30478444?dopt=Abstract

Alternate JournalNat Genet
PubMed ID30478444
PubMed Central IDPMC6481311
Grant ListR01 MH094469 / MH / NIMH NIH HHS / United States
R00 MH113823 / MH / NIMH NIH HHS / United States
MC_UU_00011/1 / MRC_ / Medical Research Council / United Kingdom
U01 MH109536 / MH / NIMH NIH HHS / United States
R01 MH101519 / MH / NIMH NIH HHS / United States
R01 MH107649 / MH / NIMH NIH HHS / United States
MC_UU_12013/4 / MRC_ / Medical Research Council / United Kingdom
U01 MH094432 / MH / NIMH NIH HHS / United States
G19/2 / MRC_ / Medical Research Council / United Kingdom
MR/L010305/1 / MRC_ / Medical Research Council / United Kingdom
K01 DK114379 / DK / NIDDK NIH HHS / United States
S10 OD018522 / OD / NIH HHS / United States
G0300189 / MRC_ / Medical Research Council / United Kingdom
/ WT_ / Wellcome Trust / United Kingdom
U01 MH109539 / MH / NIMH NIH HHS / United States