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PLoS Genet. 2011 Jun;7(6):e1002134. doi: 10.1371/journal.pgen.1002134. Epub 2011 Jun 30.

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

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1
Scripps Genomic Medicine and Scripps Translational Science Institute, La Jolla, California, United States of America.

Abstract

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.

PMID:
21738484
PMCID:
PMC3128104
DOI:
10.1371/journal.pgen.1002134
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist.

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