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.
Details
Title
Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes
Author
Smith, Erin N. : University of California San Diego Koller, Daniel L. : Indiana University Panganiban, Corrie : The Translational Genomics Research Institute Szelinger, Szabolcs : The Translational Genomics Research Institute Zhang, Peng : University of Michigan Badner, Judith A. : University of Chicago Barrett, Thomas B. : Portland VA Medical Center Berrettini, Wade H. : University of Pennsylvania Bloss, Cinnamon S. : Scripps Health Byerley, William : University of California San Francisco Coryell, William : University of Iowa Edenberg, Howard J. : Indiana University Foroud, Tatiana : Indiana University Gershon, Elliot S. : University of Chicago Greenwood, Tiffany A. : University of California San Diego Guo, Yiran : University of California San Diego Hipolito, Maria : The Children's Hospital of Pennsylvania Keating, Brendan J. : University of Pennsylvania Lawson, William B. : Howard University Liu, Chunyu : University of Chicago
Funding Information
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
Publication Date
2011-06-30
Language
English
Copyright Statement
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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.