Preprint open access publication

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

bioRxiv, Cold Spring Harbor Laboratory,


DOI:10.1101/154088, Dimensions: pub.1091917962,



  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 Queensland, grid.1003.2
  10. (10) Örebro University, grid.15895.30
  11. (11) Me, Inc., Mountain View, CA, USA
  12. (12) Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark
  13. (13) University of Copenhagen, grid.5254.6, KU
  14. (14) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  15. (15) State Serum Institute, grid.6203.7
  16. (16) Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
  17. (17) SUNY Upstate Medical University, grid.411023.5
  18. (18) University of Bergen, grid.7914.b


Abstract Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. 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 common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish population-registry data (N=77,905 cases, N=1,874,637 population controls). We find strong genetic correlation for ADHD across sex and no mean difference in polygenic burden across sex. In contrast, siblings of female probands are at an increased risk of ADHD, compared to siblings of male probands. The results also suggest that females with ADHD are at especially high risk of comorbid developmental conditions. Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity. However, autosomal common variants largely do not explain the sex bias in ADHD prevalence.


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