학술논문
Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes.
Document Type
article
Author
Erin N Smith; Daniel L Koller; Corrie Panganiban; Szabolcs Szelinger; Peng Zhang; Judith A Badner; Thomas B Barrett; Wade H Berrettini; Cinnamon S Bloss; William Byerley; William Coryell; Howard J Edenberg; Tatiana Foroud; Elliot S Gershon; Tiffany A Greenwood; Yiran Guo; Maria Hipolito; Brendan J Keating; William B Lawson; Chunyu Liu; Pamela B Mahon; Melvin G McInnis; Francis J McMahon; Rebecca McKinney; Sarah S Murray; Caroline M Nievergelt; John I Nurnberger; Evaristus A Nwulia; James B Potash; John Rice; Thomas G Schulze; William A Scheftner; Paul D Shilling; Peter P Zandi; Sebastian Zöllner; David W Craig; Nicholas J Schork; John R Kelsoe
Source
PLoS Genetics, Vol 7, Iss 6, p e1002134 (2011)
Subject
Language
English
ISSN
1553-7390
1553-7404
1553-7404
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.