Identification of Genetic Loci Shared Between Attention-Deficit/Hyperactivity Disorder, Intelligence, and Educational Attainment

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remain...

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Bibliographic Details
Published in:Biological psychiatry (1969) 2020-06, Vol.87 (12), p.1052-1062
Main Authors: O’Connell, Kevin S., Shadrin, Alexey, Smeland, Olav B., Bahrami, Shahram, Frei, Oleksandr, Bettella, Francesco, Krull, Florian, Fan, Chun C., Askeland, Ragna B., Knudsen, Gun Peggy S., Halmøy, Anne, Steen, Nils Eiel, Ueland, Torill, Walters, G. Bragi, Davíðsdóttir, Katrín, Haraldsdóttir, Gyða S., Guðmundsson, Ólafur Ó., Stefánsson, Hreinn, Reichborn-Kjennerud, Ted, Haavik, Jan, Dale, Anders M., Stefánsson, Kári, Djurovic, Srdjan, Andreassen, Ole A.
Format: Article
Language:English
Subjects:
Academic Success
ADHD
Attention Deficit Disorder with Hyperactivity - genetics
Cognition
Genetic Loci
Genetic overlap
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Intelligence - genetics
Mental health
Pleiotropy
Polymorphism, Single Nucleotide
Psychiatric disorder
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Summary:Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown. We analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment (N = 842,499), and general intelligence (N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes. We identified 58 linkage disequilibrium–independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD. These results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence.
ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2019.11.015