학술논문
Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes.
Document Type
article
Author
Smith, Erin N; Koller, Daniel L; Panganiban, Corrie; Szelinger, Szabolcs; Zhang, Peng; 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 B; McInnis, Melvin G; McMahon, Francis J; McKinney, Rebecca; Murray, Sarah S; Nievergelt, Caroline M; Nurnberger, John I; Nwulia, Evaristus A; Potash, James B; Rice, John; Schulze, Thomas G; Scheftner, William A; Shilling, Paul D; Zandi, Peter P; Zöllner, Sebastian; Craig, David W; Schork, Nicholas J; Kelsoe, John R
Source
PLoS genetics. 7(6)
Subject
Language
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.