Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia
Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia
Objective: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders.Methods: We assayed 276 publicly available ‘tag’ single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome‐wide association studies (GWAS).Results: Using gene‐based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL.Conclusions: Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.
- Oregon Health & Science University United States
- University of Oklahoma United States
- University of Pennsylvania United States
- University of Colorado System United States
- University of Oxford United Kingdom
Adult, Male, Schizoaffective disorder, Bipolar Disorder, Genotype, Bipolar disorder, Association; Bipolar disorder; Circadian; Gene; Schizoaffective disorder; Schizophrenia, Gene, Polymorphism, Single Nucleotide, Association, Young Adult, Gene Frequency, Databases, Genetic, Humans, Genetic Predisposition to Disease, Psychiatric Status Rating Scales, Circadian Rhythm Signaling Peptides and Proteins, Circadian, Middle Aged, Circadian Rhythm, Psychotic Disorders, Schizophrenia, Female, Genome-Wide Association Study
Adult, Male, Schizoaffective disorder, Bipolar Disorder, Genotype, Bipolar disorder, Association; Bipolar disorder; Circadian; Gene; Schizoaffective disorder; Schizophrenia, Gene, Polymorphism, Single Nucleotide, Association, Young Adult, Gene Frequency, Databases, Genetic, Humans, Genetic Predisposition to Disease, Psychiatric Status Rating Scales, Circadian Rhythm Signaling Peptides and Proteins, Circadian, Middle Aged, Circadian Rhythm, Psychotic Disorders, Schizophrenia, Female, Genome-Wide Association Study
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