Biological Sciences Division
Published June 30, 2011 | Version v1
Journal article Open

Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes

Creators

  • 1. University of California San Diego
  • 2. Indiana University
  • 3. The Translational Genomics Research Institute
  • 4. University of Michigan
  • 5. University of Chicago
  • 6. Portland VA Medical Center
  • 7. University of Pennsylvania
  • 8. Scripps Health
  • 9. University of California San Francisco
  • 10. University of Iowa
  • 11. The Children's Hospital of Pennsylvania
  • 12. Howard University

Description

Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5×10-7). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies.

Notes

Due to the large number of authors, only the first 20 and the University of Chicago authors are included on the above author list. Please download the article for the complete list of authors.

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Additional details

Identifiers

DOI
10.1371/journal.pgen.1002134
Other
oai:uchicago.tind.io:10899

Funding

National Institute of Mental Health
MH078151
National Institute of Mental Health
MH081804
National Institute of Mental Health
MH059567
Genetic Association Information Network
National Institute of Mental Health
Intramural Research Program
Tzedakah Foundation
National Institutes of Health
R01 MH59553
Philip and Marcia Cohen
National Institutes of Health
UL1 RR025774

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Psychiatry and Behavioral Neuroscience