PLoS Genetics (Jun 2011)

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

  • 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

DOI
https://doi.org/10.1371/journal.pgen.1002134
Journal volume & issue
Vol. 7, no. 6
p. e1002134

Abstract

Read online

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.