A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder

Martin, Joanna and Walters, Raymond K. and Demontis, Ditte and Mattheisen, Manuel and Lee, S. Hong and Robinson, Elise and Brikell, Isabell and Ghirardi, Laura and Larsson, Henrik and Lichtenstein, Paul and Eriksson, Nicholas and Mountain View, California. and Psychiatric Genomics Consortium: Adhd Subgroup, and iPsych–Broad Adhd Workgroup, and Werge, Thomas and Mortensen, Preben Bo and Pedersen, Marianne Giørtz and Mors, Ole and Nordentoft, Merete and Hougaard, David M. and Bybjerg-Grauholm, Jonas and Wray, Naomi R. and Franke, Barbara and Faraone, Stephen V. and O'Donovan, Michael C. and Thapar, Anita and Børglum, Anders D. and Neale, Benjamin M.. (2018) A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry, 83 (12). pp. 1044-1053.

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Official URL: https://edoc.unibas.ch/64625/

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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 r; g; 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.
Faculties and Departments:07 Faculty of Psychology
UniBasel Contributors:Steinhausen, Hans-Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:12 Nov 2018 17:04
Deposited On:12 Nov 2018 17:04

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