Article open access publication

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

Biological Psychiatry, Elsevier, ISSN 1873-2402

Volume 83, 12, 2018

DOI:10.1016/j.biopsych.2017.11.026, Dimensions: pub.1093136673, PMC: PMC5992329, PMID: 29325848,


Martin, Joanna * (1) (2) (3) (4)
Demontis, Ditte (5) (6)
Mattheisen, Manuel (4) (5) (6) (7)
Lee, S. Hong (8) (9) (10)
Robinson, Elise (2) (3)
Larsson, Henrik (4) (11)
Faraone, Stephen V (13) (14)
Mors, Ole (5) (17)
Werge, Thomas (5) (18) (19)

* Corresponding author



  1. (1) Cardiff University, grid.5600.3
  2. (2) Broad Institute, grid.66859.34
  3. (3) Massachusetts General Hospital, grid.32224.35
  4. (4) Karolinska Institute, grid.4714.6
  5. (5) Lundbeck Foundation, grid.452548.a
  6. (6) Aarhus University, grid.7048.b, AU
  7. (7) Stockholm Health Care Services, grid.467087.a
  8. (8) University of New England, grid.1020.3
  9. (9) University of South Australia, grid.1026.5
  10. (10) University of Queensland, grid.1003.2
  11. (11) Örebro University, grid.15895.30
  12. (12) 23andMe (United States), grid.420283.f
  13. (13) SUNY Upstate Medical University, grid.411023.5
  14. (14) University of Bergen, grid.7914.b
  15. (15) Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
  16. (16) State Serum Institute, grid.6203.7
  17. (17) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  18. (18) University of Copenhagen, grid.5254.6, KU
  19. (19) Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark


BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.


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