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

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

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,...

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Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
Materias:
Genetics
QH426-470
Acceso en línea:https://doaj.org/article/3c68f3061e9a495589546577b22507ee
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Sumario: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.

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