Genome-Wide Association of Bipolar Disorder Suggests an Enrichment of Replicable Associations in Regions near Genes
2011 | journal article. A publication with affiliation to the University of Göttingen.
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Genome-Wide Association of Bipolar Disorder Suggests an Enrichment of Replicable Associations in Regions near Genes
Smith, E. N.; Koller, D. L.; Panganiban, C.; Szelinger, S.; Zhang, P.; Badner, J. A. & Barrett, T. B. et al. (2011)
PLoS Genetics, 7(6) art. e1002134. DOI: https://doi.org/10.1371/journal.pgen.1002134
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Details
- Authors
- Smith, Erin N.; Koller, Daniel L.; Panganiban, Corrie; Szelinger, Szabolcs; Zhang, P.; Badner, Judith A.; Barrett, Thomas B.; Berrettini, Wade H.; Bloss, Cinnamon S.; Byerley, William; Coryell, William; Edenberg, Howard J.; Foroud, Tatiana; Gershon, Elliot S.; Greenwood, Tiffany A.; Guo, Yiran; Hipolito, Maria; Keating, Brendan J.; Lawson, William B.; Liu, Chunyu; Mahon, Pamela Belmonte; McInnis, Melvin G.; McMahon, Francis J.; McKinney, Rebecca; Murray, Sarah S.; Nievergelt, Caroline M.; Nurnberger, John I., Jr.; Nwulia, Evaristus A.; Potash, James B.; Rice, John; Schulze, Thomas G.; Scheftner, William A.; Shilling, Paul D.; Zandi, Peter P.; Zoellner, Sebastian; Craig, David W.; Schork, Nicholas J.; Kelsoe, John R.
- 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 x 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.
- Issue Date
- 2011
- Status
- published
- Publisher
- Public Library Science
- Journal
- PLoS Genetics
- ISSN
- 1553-7390