TY - JOUR
T1 - Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder
AU - 23andMe Research Team
AU - ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
AU - Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium
AU - Demontis, Ditte
AU - Walters, Raymond K.
AU - Martin, Joanna
AU - Mattheisen, Manuel
AU - Als, Thomas D.
AU - Agerbo, Esben
AU - Baldursson, Gísli
AU - Belliveau, Rich
AU - Bybjerg-Grauholm, Jonas
AU - Bækvad-Hansen, Marie
AU - Cerrato, Felecia
AU - Chambert, Kimberly
AU - Churchhouse, Claire
AU - Dumont, Ashley
AU - Eriksson, Nicholas
AU - Gandal, Michael
AU - Goldstein, Jacqueline I.
AU - Grasby, Katrina L.
AU - Grove, Jakob
AU - Gudmundsson, Olafur O.
AU - Hansen, Christine S.
AU - Hauberg, Mads Engel
AU - Hollegaard, Mads V.
AU - Howrigan, Daniel P.
AU - Huang, Hailiang
AU - Maller, Julian B.
AU - Martin, Alicia R.
AU - Martin, Nicholas G.
AU - Moran, Jennifer
AU - Pallesen, Jonatan
AU - Palmer, Duncan S.
AU - Pedersen, Carsten Bøcker
AU - Pedersen, Marianne Giørtz
AU - Poterba, Timothy
AU - Poulsen, Jesper Buchhave
AU - Ripke, Stephan
AU - Robinson, Elise B.
AU - Satterstrom, F. Kyle
AU - Stefansson, Hreinn
AU - Stevens, Christine
AU - Turley, Patrick
AU - Walters, G. Bragi
AU - Won, Hyejung
AU - Wright, Margaret J.
AU - Albayrak, Özgür
AU - Anney, Richard J.L.
AU - Arranz, Maria Jesús
AU - Banaschewski, Tobias J.
AU - Bau, Claiton
AU - Jan Hottenga, Jouke
N1 - Publisher Copyright:
© 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85057436335
U2 - 10.1038/s41588-018-0269-7
DO - 10.1038/s41588-018-0269-7
M3 - Article
C2 - 30478444
AN - SCOPUS:85057436335
SN - 1061-4036
VL - 51
SP - 63
EP - 75
JO - Nature Genetics
JF - Nature Genetics
IS - 1
ER -