Meta-analysis Report

Reference	Liu, Y.,2011 PMID: 20351715
Citation	Liu, Y., D. H. Blackwood, et al. (2011). "Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder." Mol Psychiatry 16(1): 2-4.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Type	Genome-wide association study

Samples	BIP (4387 cases and 6209 controls) and MDD(1695 cases and 1761 controls).BIP results are obtained from a combined analysis of samples from the UK, the US and Ireland5,6 with all subjects genotyped using Affymetrix 500K chips (Santa Clara, CA, USA).Cases meeting DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV) criteria for MDD were ascertained from clinical and community sources, and controls at low liability for MDD were selected from a community sample.There was no known subject overlap across studies (BIP subjects were from the US, the UK and Ireland, and MDD subjects were from The Netherlands)
Statistic Method	Fixed-effects meta-analysis was accomplished using a weighted z-score method.
Basic Result	We note four findings from the meta-analysis: (A)two SNPs in a 10.5-kb region of CACNA1C exceeded a genome-wide significance level of 5E-8.12 rs1006737 (P-fixed = 3.1E-08) and rs7297582 (P-fixed =3.4E-08).Second, two ANK3 SNPs exceeded genome-wide significance in the initial BIP report but were not supported in the MDD genome-wide association study (rs10994336 and rs10994338 with P-values ~0.9). Third, support for the PCLO SNP of particular interest in the MDD genome-wide association study (rs2522843) was not increased with meta-analysis although several SNPs had P-values < 0.05. Fourth, several areas were of modest significance in each primary genome-wide association study and of considerably greater significance in the meta-analysis (although none reached the genome-wide significance level): intergenic regions on chromosome 2: 175.95-175.99Mb and chromosome 13:49.96-49.98Mb along with SNPs in SYNE1, FAT4, DMTF1, C7orf23 and C15orf53. SYNE1 (a gene mutated in spinocerebellar ataxia) is of immediate interest as it contains a spectrin-binding domain, suggesting a connection with the function of the BIP susceptibility locus ANK3.In conclusion, this analysis provides support for a role of CACNA1C risk variants for both bipolar and unipolar major mood disorders.