Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.US National Institutes of Health (NIH) MH078151 MH081804 MH059567 MH59553 MH080372 1U54RR025204 Genetic Association Information Network (GAIN) NIMH Intramural Research Program Tzedakah Foundation American Philosophical Society Stardust foundation National Library of Medicine Stanley Foundation for Medical Research Wellcome Trust Pritzker Neuropsychiatric Disorders Research Fund L.L.C. GlaxoSmithKline Research Council of Norway 167153/V50 163070/V50 175345/V50 South-East Norway Health Authority 123-2004 EU (ENBREC