A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder

Martin, Joanna, Walters, Raymond K., Demontis, Ditte, Mattheisen, Manuel, Lee, S. Hong, Robinson, Elise, Brikell, Isabell, Ghirardi, Laura, Larsson, Henrik, Lichtenstein, Paul, Eriksson, Nicholas, 23andMe Research Team, Psychiatric Genomics Consortium: ADHD Subgroup, iPSYCH–Broad ADHD Workgroup, Werge, Thomas, Mortensen, Preben Bo, Pedersen, Marianne Giørtz, Mors, Ole, Nordentoft, Merete, Hougaard, David M., Bybjerg-Grauholm, Jonas, Wray, Naomi R., Franke, Barbara, Faraone, Stephen V., O'Donovan, Michael C., Thapar, Anita, Børglum, Anders D. and Neale, Benjamin M. (2017) A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder. Biological Psychiatry, . doi:10.1016/j.biopsych.2017.11.026

Author Martin, Joanna
Walters, Raymond K.
Demontis, Ditte
Mattheisen, Manuel
Lee, S. Hong
Robinson, Elise
Brikell, Isabell
Ghirardi, Laura
Larsson, Henrik
Lichtenstein, Paul
Eriksson, Nicholas
23andMe Research Team
Psychiatric Genomics Consortium: ADHD Subgroup
iPSYCH–Broad ADHD Workgroup
Werge, Thomas
Mortensen, Preben Bo
Pedersen, Marianne Giørtz
Mors, Ole
Nordentoft, Merete
Hougaard, David M.
Bybjerg-Grauholm, Jonas
Wray, Naomi R.
Franke, Barbara
Faraone, Stephen V.
O'Donovan, Michael C.
Thapar, Anita
Børglum, Anders D.
Neale, Benjamin M.
Title A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 1873-2402
Publication date 2017-12-02
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2017.11.026
Open Access Status DOI
Place of publication Philadelphia, PA United States
Publisher Elsevier
Language eng
Subject 2803 Biological Psychiatry
Abstract Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.

We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls).

Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15).

Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.
Keyword ADHD
Neurodevelopmental disorders
Polygenic risk score analysis
Sex bias
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
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Created: Wed, 17 Jan 2018, 12:09:10 EST