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

• Published in: Biological psychiatry (1969) Vol. 87; no. 12; pp. 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: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.2020
• 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; ADHD; Pleiotropy; Cognition; Mental health; Genetic overlap; Psychiatric disorder
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2019.11.015

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.