Genome-Wide Association Study of Bipolar Disorder in European Americans J. Li1, L.J. Scott3, D.
Absher1, R.C. Thompson4, W. Guan3, F. Meng5, A. Southwick1, M. Burmeister4,5, H. Akil5, S.J. Watson5, R.
M. Myers2, M. Boehnke3. 1) Stanford Human Genome Center; 2) Department of Genetics, Stanford
University, Palo Alto, CA; 3) Department of Biostatistics and Center for Statistical Genetics; 4)
Department of Psychiatry; 5) Molecular and Behavioral Neuroscience Institute, University of Michigan,
Ann Arbor, MI.
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.
The authors are members of the Pritzker Neuropsychiatric Disorders Research Consortium, which is
supported by the Pritzker Neuropsychiatric Disorders Research Fund L.L.C.