Nature genetics · 2018

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

СтатьяМетаанализПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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Demontis Ditte, Walters Raymond K, Martin Joanna, Mattheisen Manuel, Als Thomas D, Agerbo Esben, Baldursson Gísli, Belliveau Rich, Bybjerg-Grauholm Jonas, Bækvad-Hansen Marie, Cerrato Felecia, Chambert Kimberly, Churchhouse Claire, Dumont Ashley, Eriksson Nicholas, Gandal Michael, Goldstein Jacqueline I, Grasby Katrina L, Grove Jakob, Gudmundsson Olafur O, Hansen Christine S, Hauberg Mads Engel, Hollegaard Mads V, Howrigan Daniel P, Huang Hailiang, Maller Julian B, Martin Alicia R, Martin Nicholas G, Moran Jennifer, Pallesen Jonatan, Palmer Duncan S, Pedersen Carsten Bøcker, Pedersen Marianne Giørtz, Poterba Timothy, Poulsen Jesper Buchhave, Ripke Stephan, Robinson Elise B, Satterstrom F Kyle, Stefansson Hreinn, Stevens Christine, Turley Patrick, Walters G Bragi, Won Hyejung, Wright Margaret J, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Andreassen Ole A, Asherson Philip, Burton Christie L, Boomsma Dorret I, Cormand Bru, Dalsgaard Søren, Franke Barbara, Gelernter Joel, Geschwind Daniel, Hakonarson Hakon, Haavik Jan, Kranzler Henry R, Kuntsi Jonna, Langley Kate, Lesch Klaus-Peter, Middeldorp Christel, Reif Andreas, Rohde Luis Augusto, Roussos Panos, Schachar Russell, Sklar Pamela, Sonuga-Barke Edmund J S, Sullivan Patrick F, Thapar Anita, Tung Joyce Y, Waldman Irwin D, Medland Sarah E, Stefansson Kari, Nordentoft Merete, Hougaard David M, Werge Thomas, Mors Ole, Mortensen Preben Bo, Daly Mark J, Faraone Stephen V, Børglum Anders D, Neale Benjamin M

Аннотация

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.

Предметные рубрики MeSH

Adolescent 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

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH