Preprint open access publication

A genome-wide association study for shared risk across major psychiatric disorders in a nation-wide birth cohort implicates fetal neurodevelopment as a key mediator

bioRxiv, Cold Spring Harbor Laboratory,

2017

DOI:10.1101/240911, Dimensions: pub.1100115880,

Affiliations

Organisations

  1. (1) Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Denmark
  2. (2) Lundbeck Foundation, grid.452548.a
  3. (3) University of California, Los Angeles, grid.19006.3e
  4. (4) University of Geneva, grid.8591.5
  5. (5) State Serum Institute, grid.6203.7
  6. (6) Aarhus University, grid.7048.b, AU
  7. (7) Broad Institute, grid.66859.34
  8. (8) Massachusetts General Hospital, grid.32224.35
  9. (9) Copenhagen Mental Health Center, Mental Health Services Capital Region of Denmark Copenhagen, Denmark
  10. (10) University of Copenhagen, grid.5254.6, KU
  11. (11) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  12. (12) University of California, San Diego, grid.266100.3

Description

Abstract There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here, we leverage the unique iPSYCH study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder SNP-heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during midgestation. This epoch is supported by partitioning cross-disorder SNP-heritability which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings indicate that dysregulation of genes that direct neurodevelopment by common genetic variants results in general liability for many later psychiatric outcomes.

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Aarhus University

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Times Cited: 9

Field Citation Ratio (FCR): 1.91

Open Access Info

Green, Published