Preprint open access publication

Common risk variants identified in autism spectrum disorder

bioRxiv, Cold Spring Harbor Laboratory,

2017

DOI:10.1101/224774, Dimensions: pub.1093027859,

Authors

Grove, Jakob (1) (2)
Ripke, Stephan (3) (4) (5)
Als, Thomas D. (1) (2)
Won, Hyejung (1) (6)
Agerbo, Esben (1) (2)
Demontis, Ditte (1) (2)
Hansen, Christine S. (1) (11) (14)
Hope, Sigrun (7) (8)
Huang, Hailiang (4) (5)
Maller, Julian (4) (15)
Martin, Joanna (2) (4) (9)
Nyegaard, Mette (1) (2)
Nærland, Terje (7) (8)
Palotie, Aarno (4) (5) (16)
St Pourcain, Beate (17) (18) (19)
Qvist, Per (1) (2)
Roussos, Panos (10) (23)
Sandin, Sven (10) (12)
Turley, Patrick (4) (5)
Walters, G. Bragi (25) (27)
Xu, Xinyi (10)
Werge, Thomas (1) (14) (28)
Mors, Ole (1) (29)
Daly, Mark J. * (4) (5)

* Corresponding author

Affiliations

Organisations

  1. (1) Lundbeck Foundation, grid.452548.a
  2. (2) Aarhus University, grid.7048.b, AU
  3. (3) Charité, grid.6363.0
  4. (4) Broad Institute, grid.66859.34
  5. (5) Massachusetts General Hospital, grid.32224.35
  6. (6) University of California, Los Angeles, grid.19006.3e
  7. (7) NORMENT - KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway
  8. (8) Oslo University Hospital, grid.55325.34
  9. (9) Cardiff University, grid.5600.3
  10. (10) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  11. (11) State Serum Institute, grid.6203.7
  12. (12) Department of Medical Epidemiology and Biostatistics, Karolinska, Sweden
  13. (13) University of Pittsburgh, grid.21925.3d
  14. (14) Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Denmark
  15. (15) Genomics plc, Oxford, UK
  16. (16) University of Helsinki, grid.7737.4
  17. (17) Max Planck Institute for Psycholinguistics, grid.419550.c
  18. (18) Radboud University Nijmegen, grid.5590.9
  19. (19) University of Bristol, grid.5337.2
  20. (20) Wellcome Sanger Institute, grid.10306.34
  21. (21) Boston University, grid.189504.1
  22. (22) Carnegie Mellon University, grid.147455.6
  23. (23) James J Peters VA Medical Center, grid.274295.f
  24. (24) The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kópavogur, Iceland
  25. (25) CODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland
  26. (26) University of North Carolina System, grid.410711.2
  27. (27) University of Iceland, grid.14013.37
  28. (28) University of Copenhagen, grid.5254.6, KU
  29. (29) Aarhus University Hospital, grid.154185.c, Central Denmark Region

Description

Abstract Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes, in contrast to what is typically seen in other complex disorders. These results highlight biological insights, particularly relating to neuronal function and corticogenesis and establish that GWAS performed at scale will be much more productive in the near term in ASD, just as it has been in a broad range of important psychiatric and diverse medical phenotypes.

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Times Cited: 78

Field Citation Ratio (FCR): 16.52

Open Access Info

Green, Published