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Sex-specific manifestation of genetic risk for attention deficit hyperactivity disorder in the general population

Journal article
Authors J. Martin
M. J. Taylor
M. Rydell
L. Riglin
O. Eyre
Y. Lu
Sebastian Lundström
H. Larsson
A. Thapar
P. Lichtenstein
Published in Journal of Child Psychology and Psychiatry
Volume 59
Issue 8
Pages 908-916
ISSN 0021-9630
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Gillberg Neuropsychiatry Centre
Centre for Ethics, Law, and Mental Health
Pages 908-916
Language en
Keywords ADHD, anxiety, depression, genetics, CATSS, ALSPAC, deficit/hyperactivity disorder, gender-differences, adhd, twin, children, prevalence, anxiety, epidemiology, association, adolescents, Psychology, Psychiatry, netics, v171, p931
Subject categories Neurosciences


Background: Attention deficit hyperactivity disorder (ADHD) is more commonly diagnosed in males than in females. A growing body of research suggests that females with ADHD might be underdiagnosed or receive alternative diagnoses, such as anxiety or depression. Other lines of reasoning suggest that females might be protected from developing ADHD, requiring a higher burden of genetic risk to manifest the disorder. Methods: We tested these two hypotheses, using common variant genetic data from two population-based cohorts. First, we tested whether females and males diagnosed with anxiety or depression differ in terms of their genetic risk for ADHD, assessed as polygenic risk scores (PRS). Second, we tested whether females and males with ADHD differed in ADHD genetic risk burden. We used three different diagnostic definitions: registry-based clinical diagnoses, screening-based research diagnoses and algorithm-based research diagnoses, to investigate possible referral biases. Results: In individuals with a registry-based clinical diagnosis of anxiety or depression, females had higher ADHD PRS than males [OR(CI) = 1.39 (1.12-1.73)] but there was no sex difference for screening-based [OR(CI) = 1.15 (0.94-1.42)] or algorithm-based [OR(CI) = 1.04 (0.89-1.21)] diagnoses. There was also no sex difference in ADHD PRS in individuals with ADHD diagnoses that were registry-based [OR(CI) = 1.04 (0.84-1.30)], screening-based [OR(CI) = 0.96 (0.85-1.08)] or algorithm-based [OR(CI) = 1.15 (0.78-1.68)]. Conclusions: This study provides genetic evidence that ADHD risk may be more likely to manifest or be diagnosed as anxiety or depression in females than in males. Contrary to some earlier studies, the results do not support increased ADHD genetic risk in females with ADHD as compared to affected males.

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