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

Kevin S O'Connell; Alexey Shadrin; Olav B Smeland; Shahram Bahrami; Oleksandr Frei; Francesco Bettella; Florian Krull; Chun C Fan; Ragna B Askeland; Gun Peggy S Knudsen; Anne Halmøy; Nils Eiel Steen; Torill Ueland; G Bragi Walters; Katrín Davíðsdóttir; Gyða S Haraldsdóttir; Ólafur Ó Guðmundsson; Hreinn Stefánsson; Ted Reichborn-Kjennerud; Jan Haavik; Anders M Dale; Kári Stefánsson; Srdjan Djurovic; Ole A Andreassen

doi:10.1016/j.biopsych.2019.11.015

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

Biol Psychiatry. 2020 Jun 15;87(12):1052-1062. doi: 10.1016/j.biopsych.2019.11.015. Epub 2019 Nov 29.

Authors

Kevin S O'Connell¹, Alexey Shadrin², Olav B Smeland², Shahram Bahrami², Oleksandr Frei², Francesco Bettella², Florian Krull², Chun C Fan³, Ragna B Askeland⁴, Gun Peggy S Knudsen⁵, Anne Halmøy⁶, Nils Eiel Steen², Torill Ueland⁷, G Bragi Walters⁸, Katrín Davíðsdóttir⁹, Gyða S Haraldsdóttir⁹, Ólafur Ó Guðmundsson¹⁰, Hreinn Stefánsson¹¹, Ted Reichborn-Kjennerud¹², Jan Haavik¹³, Anders M Dale¹⁴, Kári Stefánsson⁸, Srdjan Djurovic¹⁵, Ole A Andreassen¹⁶

Affiliations

¹ Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. Electronic address: kevin.oconnell@medisin.uio.no.
² Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
³ Department of Radiology, University of California, San Diego, La Jolla, California; Department of Cognitive Science, University of California, San Diego, La Jolla, California.
⁴ Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
⁵ Division of Health Data and Digitalisation, Norwegian Institute of Public Health, Oslo, Norway.
⁶ Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
⁷ Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁸ deCODE Genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁹ The Centre for Child Development and Behaviour, Capital Area Primary Health Care, Reykjavik, Iceland.
¹⁰ deCODE Genetics/Amgen, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Child and Adolescent Psychiatry, National University Hospital, Reykjavik, Iceland.
¹¹ deCODE Genetics/Amgen, Reykjavik, Iceland.
¹² Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
¹³ Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway; Department of Biomedicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
¹⁴ Department of Radiology, University of California, San Diego, La Jolla, California; Department of Psychiatry, University of California, San Diego, La Jolla, California; Department of Neurosciences, University of California, San Diego, La Jolla, California; Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California.
¹⁵ Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
¹⁶ Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. Electronic address: o.a.andreassen@medisin.uio.no.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ADHD; Cognition; Genetic overlap; Mental health; Pleiotropy; Psychiatric disorder.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Academic Success*
Attention Deficit Disorder with Hyperactivity* / genetics
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Intelligence / genetics
Polymorphism, Single Nucleotide

Abstract

Publication types

MeSH terms

Grants and funding