Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia.
We hypothesize that circadian dysfunction could underlie, at least partially, the liability for bipolar 1 disorder (BD1). Our hypothesis motivated tests for the association between the polymorphisms of genes that mediate circadian function and liability for BD1. The US Caucasian patients with BD1 (DSM-IV criteria) and available parents were recruited from Pittsburgh and surrounding areas (n = 138 cases, 196 parents) and also selected from the NIMH Genetics Collaborative Initiative (n = 96 cases, 192 parents). We assayed 44 informative single-nucleotide polymorphisms (SNPs) from eight circadian genes in the BD1 samples. A population-based sample, specifically cord blood samples from local live births, served as community-based controls (n = 180). It was used as a contrast for genotype and haplotype distributions with those of patients. US patients with schizophrenia/schizoaffective disorder (SZ/SZA, n = 331) and available parents from Pittsburgh (n = 344) were assayed for a smaller set of SNPs based on the results from the BD1 samples. 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.
Mansour
H A
HA
Departments of Psychiatry and Human Genetics, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, PA, USA.
Wood
J
J
Logue
T
T
Chowdari
K V
KV
Dayal
M
M
Kupfer
D J
DJ
Monk
T H
TH
Devlin
B
B
Nimgaonkar
V L
VL
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001683:Biological Clocks / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D021081:Chronobiology Disorders / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D056950:Period Circadian Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics / Q000503:physiopathology; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C512644:PER3 protein, human; C509769:TIMELESS protein, human; C509770:Timeless protein, mouse