Preprint open access publication

Discovery of the first genome-wide significant risk loci for ADHD

bioRxiv, Cold Spring Harbor Laboratory,

2017

DOI:10.1101/145581, Dimensions: pub.1085865583,

Authors

Demontis, Ditte (1) (2)
Martin, Joanna (4) (5) (6)
Mattheisen, Manuel (1) (2) (5) (7)
Als, Thomas D. (1) (2)
Agerbo, Esben (1) (2)
Grove, Jakob (1) (2)
Hansen, Christine S. (2) (8) (11)
Huang, Hailiang (3) (4)
Maller, Julian (4) (12)
Ripke, Stephan (3) (4) (13)
Turley, Patrick (3) (4)
Boomsma, Dorret (17) (18)
Cormand, Bru (19) (20) (21)
Gelernter, Joel (23) (24)
Kranzler, Henry (26) (27)
Lesch, Klaus-Peter (29) (30)
Middeldorp, Christel (18) (31) (32)
Rohde, Luis A. (34) (35)
Roussos, Panos (36) (37)
Sonuga-Barke, Edmund (28) (38) (39)
Werge, Thomas (2) (11) (41)
Mors, Ole (2) (42)
Daly, Mark J. (3) (4)
Neale, Benjamin M. * (3) (4)

* Corresponding author

Affiliations

Organisations

  1. (1) Aarhus University, grid.7048.b, AU
  2. (2) Lundbeck Foundation, grid.452548.a
  3. (3) Massachusetts General Hospital, grid.32224.35
  4. (4) Broad Institute, grid.66859.34
  5. (5) Karolinska Institute, grid.4714.6
  6. (6) Cardiff University, grid.5600.3
  7. (7) Stockholm Health Care Services, grid.467087.a
  8. (8) State Serum Institute, grid.6203.7
  9. (9) Metabolomx (United States), grid.435694.9
  10. (10) University of California, Los Angeles, grid.19006.3e
  11. (11) Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark
  12. (12) Genomics plc, Oxford, United Kingdom
  13. (13) Charité, grid.6363.0
  14. (14) Boston University, grid.189504.1
  15. (15) Oslo University Hospital, grid.55325.34
  16. (16) University of Toronto, grid.17063.33
  17. (17) EMGO Institute for Health and Care Research, grid.466632.3
  18. (18) Amsterdam Neuroscience, grid.484519.5
  19. (19) Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
  20. (20) University of Barcelona, grid.5841.8
  21. (21) Hospital Sant Joan de Déu Barcelona, grid.411160.3
  22. (22) Departments of Human Genetics (855) and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands
  23. (23) Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut, USA
  24. (24) Yale University, grid.47100.32
  25. (25) Children's Hospital of Philadelphia, grid.239552.a
  26. (26) National Institutes of Health Clinical Center, grid.410305.3
  27. (27) University of Pennsylvania, grid.25879.31
  28. (28) King's College London, grid.13097.3c
  29. (29) Maastricht University, grid.5012.6
  30. (30) University of Würzburg, grid.8379.5
  31. (31) Child and Youth Mental Health Service, Children’s Health Queensland Hospital and Health Service, Brisbane, Australia
  32. (32) University of Queensland, grid.1003.2
  33. (33) University Hospital Frankfurt, grid.411088.4
  34. (34) Federal University of Rio Grande do Sul, grid.8532.c
  35. (35) Hospital de Clínicas de Porto Alegre, grid.414449.8
  36. (36) James J Peters VA Medical Center, grid.274295.f
  37. (37) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  38. (38) Ghent University, grid.5342.0
  39. (39) University of Southampton, grid.5491.9
  40. (40) University of North Carolina System, grid.410711.2
  41. (41) University of Copenhagen, grid.5254.6, KU
  42. (42) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  43. (43) SUNY Upstate Medical University, grid.411023.5

Description

Abstract Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of school-age children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no individual variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 ADHD cases and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, revealing new and important information on the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes, as well as around brain-expressed regulatory marks. These findings, based on clinical interviews and/or medical records are supported by additional analyses of a self-reported ADHD sample and a study of quantitative measures of ADHD symptoms in the population. Meta-analyzing these data with our primary scan yielded a total of 16 genome-wide significant loci. The results support the hypothesis that clinical diagnosis of ADHD is an extreme expression of one or more continuous heritable traits.

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Times Cited: 158

Field Citation Ratio (FCR): 33.46

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Green, Published