Genome-Wide Association Study of Bipolar Disorder in European Americans
J. Li; L.J. Scott; D. Absher; R.C. Thompson; W. Guan; F. Meng; A. Southwick; M. Burmeister,; H. Akil; S.J. Watson; R. M. Myers; M. Boehnke
American Society of Human Genetics. 2007.
Bipolar disorder (BPD) is a common familial disease with poorly understood etiology. Despite clear evidence for a substantial genetic contribution, linkage and candidate gene studies have so far failed to generate well-replicated findings. We have performed a genome-wide association study of BPD in which we used the Illumina Infinium Beadchips to genotype >550,000 "tagging SNPs" in European American samples. We obtained from the NIMH Genetic Repository program ~1,200 Bipolar I cases, up to two BPD cases per sibship, and ~800 unrelated controls who reported no BPD, schizophrenia, or major depression. Cases and controls were frequency-matched by self-reported ancestry from different regions of Europe. The analysis of the first 466 cases and 467 controls showed that >99% of the samples had initial call rates of >98.5%, and >99.5% of SNPs passed all QC measures. Inferred ancestry showed reasonable agreement with self-reported ancestry, and confirmed adequate sample matching, with a genomic control inflation factor of 1.02. Allelic intensity data revealed extensive copy number variation (CNV), covering a broad range of CNV sizes and population frequencies. We have now completed genotyping for the ~2,000 samples; and data cleaning and association analysis is currently underway for the entire dataset. To increase statistical power, we will augment our analysis with publicly-available control datasets for Americans of European ancestry.