期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
卷 141B, 期 3, 页码 234-241出版社
WILEY
DOI: 10.1002/ajmg.b.30252
关键词
manic-depressive illness; genetic linkage; genetic association; PER3; BMAL1
资金
- Intramural NIH HHS Funding Source: Medline
- NCRR NIH HHS [M01 RR00827, M01 RR000827] Funding Source: Medline
- NHLBI NIH HHS [HL61280, R56 HL071123, HL074730-02, R56 HL071123-04, HL070137-01A1, R01 HL070137, HL071123, HL054998-09, R01 HL074730, HL069758-03, R01 HL071123, U01 HL069758, U01 HL064777, P50 HL054998, HL064777-06] Funding Source: Medline
- NIA NIH HHS [R01 AG015763, R01 AG012364, AG023122-01, AG15763, AG12364, U19 AG023122] Funding Source: Medline
- NIDA NIH HHS [DA13769] Funding Source: Medline
- NIMH NIH HHS [K08 MH067959, MH059567-05A2, MH59567, R01 MH068503, U01 MH46274, MH068503-01A1, MH067959, UO1 MH46282, MH68503, UO1 MH46280, R01 MH059567, MH47612] Funding Source: Medline
- PHS HHS [HLMH065571-02] Funding Source: Medline
Bipolar affective disorder (BPAD) is suspected to arise in part from malfunctions of the circadian system, a system that enables adaptation to a daily and seasonally cycling environment. Genetic variations altering functions of genes involved with the input to the circadian clock, in the molecular feedback loops constituting the circadian oscillatory mechanism itself, or in the regulatory output systems could influence BPAD as a result. Several human circadian system genes have been identified and localized recently, and a comparison with linkage hotspots for BPAD has revealed some correspondences. We have assessed evidence for linkage and association involving polymorphisms in 10 circadian clock genes (ARNTL, CLOCK, CRY2, CSNK1 epsilon, DBP, GSK3 beta, NPAS2, PERI, PER2, and PER3) to BPAD. Linkage analysis in 52 affected families showed suggestive evidence for linkage to CSNK1 epsilon This finding was not substantiated in the association study. Fifty-two SNPs in 10 clock genes were genotyped in 185 parent proband triads. Single SNP TDT analyses showed no evidence for association to BPAD. However, more powerful haplotype analyses suggest two candidates deserving further studies. Haplotypes in ARNTL and PER3 were found to be significantly associated with BPAD via single-gene permutation tests (P-G = 0.025 and 0.008, respectively). The most suggestive haplotypes in PER3 showed a Bonferroni-corrected P-value of P-GC = 0.07. These two genes have previously been implicated in circadian rhythm sleep disorders and affective disorders. With correction for the number of genes considered and tests conducted, these data do not provide statistically significant evidence for association. However, the trends for ARNTL and PER3 are suggestive of their involvement in bipolar disorder and warrant further study in a larger sample. (c) 2006 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据