Whole-genome association study of bipolar disorder.

We performed a genome wide association scan in 1,461 patients with bipolar 1 disorder and 2,008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and University College London sample collections with successful genotyping for 372,193 SNPs. Our strongest single SNP results are found in myosin5B (MYO5B; p=1.66 × 10−7) and tetraspanin-8 (TSPAN8; p=6.11 × 10−7). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; p=2.04 × 10−8, TSPAN8; p=7.57 × 10−7 and EGFR; p=8.36 × 10−8). For replication, we genotyped 304 SNPs in a family-based NIMH sample (n=409 trios) and a University of Edinburgh case-control sample (n=365 cases, 351 controls) which do not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1,868 patients with bipolar disorder and 2,938 controls completed as part of the Wellcome Trust Case-Control Consortium (1) indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene, but no other single SNP associations are highly significant in both studies. Given the heritability of bipolar disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.