Study Report

Reference	Mansour, H. A., 2006 PMID: 16507006
Citation	Mansour, H. A., J. Wood, et al. (2006). "Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia." Genes Brain Behav 5(2): 150-157.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	Pittsburgh sample: 138 cases and 196 parents; NIMH Genetics Collaborative Initiative: 96 cases and 192 parents; 180 community-based controls; 331 US patients with schizophrenia/schizoaffective disorder and 344 available parents from Pittsburgh
SNP/Region/Marker Size	46 SNPs
Predominant Ethnicity	Caucasian
Population	American

Sample Diagnosis	DSM-IV
Sample Status	For Pittsburgh-based samples, individuals with BD1, SZ or SZA (DSM-IV criteria) and their available parents participated. Additional clinical information was obtained from available clinical records and from relatives. Pedigrees having probands with BD1 (DSM-IV criteria) were ascertained at Indiana University, Johns Hopkins University, Washington University and the Clinical Neurogenetics Branch of the NIMH Intramural Research Program. The DIGS was the primary interview schedule. The families were ascertained if they included two or more affected first-degree relatives. Pedigrees are sequentially extended through first-degree relatives of specific individuals with specific diagnoses. Pedigrees in which both parents of the proband have SAB (SZA, bipolar type) or BD1 are excluded.
Technique	genotyping using multiplex PCR
Statistical Method	Transmission distortion at individual SNPs was tested initially using the transmission disequilibrium test (TDT) as implemented in the GENEHUNTER software package. To evaluate whether the genotype distribution differed significantly among individuals diagnosed with BD1 vs. the population in general, they contrasted the observed genotyped distribution for cases with the sample from neonates by using the Cochran-Armitage trend test.
Result Summary	Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples. The associations were detected using family-based and case-control analyses, albeit with different SNPs. Associations with TIMELESS and PERIOD3 were also detected in the Pittsburgh SZ/SZA group. Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here.