Genome-wide Association Analysis Identifies 14 New Risk Loci for Schizophrenia

Schizophreniais a heritabledisorder with substantial public health impact. We conducted a multistage genome-wide association study(GWAS) for schizophreniabeginning with a Swedish national sample (5,001 cases, 6,243 controls) followed by meta-analysis with prior schizophreniaGWAS (8,832 cases, 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls, and 581 trios). In total, 22 regions met genome-wide significance (14 novel and one previously implicated in bipolar disorder). The results strongly implicate calcium signalingin the etiology of schizophrenia, and include genomewide significant results for CACNA1C and CACNB2 whose protein products interact. We estimate that ~8,300 independent and predominantly common SNPs contribute to risk for schizophreniaand that these collectively account for most of its heritability. Common genetic variation plays an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this devastating disorder.