Article open access publication

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance

The British Journal of Psychiatry, Royal College of Psychiatrists, ISSN 0007-1250

Volume 208, 2, 2016

DOI:10.1192/bjp.bp.114.156976, Dimensions: pub.1064192016, PMC: PMC4829352, PMID: 26338991,



  1. (1) Kunming Institute of Zoology, grid.419010.d
  2. (2) Johns Hopkins University, grid.21107.35
  3. (3) Karolinska Institute, grid.4714.6
  4. (4) Broad Institute, grid.66859.34
  5. (5) Shanghai Jiao Tong University, grid.16821.3c
  6. (6) Aarhus University, grid.7048.b, AU
  7. (7) University of Basel, grid.6612.3
  8. (8) University of Bonn, grid.10388.32
  9. (9) Central Institute of Mental Health, grid.413757.3
  10. (10) Spitalul Clinic de Psihiatrie Alexandru Obregia, grid.440274.1
  11. (11) University of California, San Francisco, grid.266102.1
  12. (12) Beijing Normal University, grid.20513.35
  13. (13) University of California, Irvine, grid.266093.8
  14. (14) Mondor Institute of Biomedical Research, grid.462410.5
  15. (15) Inserm U 955, IMRB, Psychiatrie Génétique, and Fondation Fondamental, Créteil, AP-HP, Groupe hospitalier Lariboisière – F. Widal, Pôle de Psychiatrie, Paris, and Université Paris Diderot, Paris, France
  16. (16) Fondation FondaMental, grid.484137.d
  17. (17) University Hospital of Lausanne, grid.8515.9
  18. (18) Institute of Social and Preventive Medicine, grid.482968.9
  19. (19) UNSW Sydney, grid.1005.4
  20. (20) Neuroscience Research Australia, Sydney and School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia
  21. (21) QIMR Berghofer Medical Research Institute, grid.1049.c
  22. (22) University of Illinois at Chicago, grid.185648.6


BACKGROUND: Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. AIMS: We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. METHOD: To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals. RESULTS: Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85 × 10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54 × 10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. CONCLUSIONS: Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.


Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

Aarhus University

Dimensions Citation Indicators

Times Cited: 10

Field Citation Ratio (FCR): 2.65

Relative Citation ratio (RCR): 0.47

Open Access Info