Testing the role of circadian genes in conferring risk for psychiatric disorders

Disturbed sleep and disrupted circadian rhythms are a common feature of psychiatric disorders, and many groups have postulated an association between genetic variants in circadian clock genes and psychiatric disorders. Using summary data from the association analyses of the Psychiatric Genomics Consortia (PGC) for schizophrenia, bipolar disorder and major depressive disorder, we evaluated the evidence that common SNPs in genes encoding components of the molecular clock influence risk to psychiatric disorders. Initially, gene-based and SNP P-values were analyzed for 21 core circadian genes. Subsequently, an expanded list of genes linked to control of circadian rhythms was analyzed. After correcting for multiple comparisons, none of the circadian genes were significantly associated with any of the three disorders. Several genes previously implicated in the etiology of psychiatric disorders harbored no SNPs significant at the nominal level of P < 0.05, and none of the the variants identified in candidate studies of clock genes that were included in the PGC datasets were significant after correction for multiple testing. There was no evidence of an enrichment of associations in genes linked to control of circadian rhythms in human cells. Our results suggest that genes encoding components of the molecular clock are not good candidates for harboring common variants that increase risk to bipolar disorder, schizophrenia, or major depressive disorder.