Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm.
Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm.
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DOI：
10.1002/ajmg.b.30714
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发表时间：
2008-10-05
期刊：
影响因子：
--
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Shi J;Wittke-Thompson JK;Badner JA;Hattori E;Potash JB;Willour VL;McMahon FJ;Gershon ES;Liu C
一些先前的研究表明，昼夜节律的功能障碍可能会增加双相情感障碍（BP）的易感性。我们对五个昼夜节律基因进行了关联研究（1992，PER 1 -3，和TIMELESS）在36个三重奏和79个四重奏的家庭收藏中（样品I）和10个昼夜节律基因（ARNTL、ARNTL 2、BHLHB 2、BHLHB 3、CLOCK、CSNK 1D、CSNK 1 E、DBP和NR 1D 1）在70个三联体和237个四联体的大家族集合中的表达（样本II），其中包括与样本I相同的114个家庭，但不一定是相同的个体。在样品II中，同胞传递不平衡检验（Sibling-Transmission Disequilibrium Test，sib-tdt）分析显示BP与CLOCK基因内或附近的三个SNP名义上显著相关（rs 534654，p = 0.0097; rs6850524，p = 0.012; rs 4340844，p = 0.015）。此外，ARNTL 2、CLOCK、DBP和TIMELESS基因中的SNP以及ARNTL、CLOCK、CSNK 1 E和TIMELESS基因中的单倍型显示出与BP患者中鉴定的几种昼夜节律表型相关的提示性证据。然而，这些协会没有达到全基因或实验范围内的意义后，多重检验校正。然而，BHLHB 2 5′上游的rs6442925、CSNK 1 E的rs 1534891和CLOCK基因3′端附近的rs 534654之间的多位点相互作用与BP显著相关（p = 0.00000172）。在使用错误发现率方法校正多次测试后，它仍然显着。我们的研究结果表明，在双相情感障碍的易感性的三个昼夜节律基因之间的相互作用。
Several previous studies suggest that dysfunction of circadian rhythms may increase susceptibility to bipolar disorder (BP). We conducted an association study of five circadian genes (CRY2, PER1-3, and TIMELESS) in a family collection of 36 trios and 79 quads (Sample I), and 10 circadian genes (ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CSNK1D, CSNK1E, DBP, and NR1D1) in an extended family collection of 70 trios and 237 quads (Sample II), which includes the same 114 families but not necessarily the same individuals as Sample I. In Sample II, the Sibling-Transmission Disequilibrium Test (sib-tdt) analysis showed nominally significant association of BP with three SNPs within or near the CLOCK gene (rs534654, p = 0.0097; rs6850524, p = 0.012; rs4340844, p = 0.015). In addition, SNPs in the ARNTL2, CLOCK, DBP, and TIMELESS genes and haplotypes in the ARNTL, CLOCK, CSNK1E, and TIMELESS genes showed suggestive evidence of association with several circadian phenotypes identified in BP patients. However, none of these associations reached gene-wide or experiment-wide significance after correction for multiple-testing. A multi-locus interaction between rs6442925 in the 5′ upstream of BHLHB2, rs1534891 in CSNK1E, and rs534654 near the 3′ end of the CLOCK gene, however, is significantly associated with BP (p = 0.00000172). It remains significant after correcting for multiple testing using the False Discovery Rate method. Our results indicate an interaction between three circadian genes in susceptibility to bipolar disorder.
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影响因子：
2.5
作者：
Benedetti, F.;Radaelli, D.;Smeraldi, E.
通讯作者：
Smeraldi, E.
影响因子：
2.1
作者：
Dudbridge, F
通讯作者：
Dudbridge, F
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
2.5
作者：
Benedetti, F;Serretti, A;Smeraldi, B
通讯作者：
Smeraldi, B
DOI：
10.1073/pnas.0508483103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Cohen, JC;Pertsemlidis, A;Hobbs, HH
通讯作者：
Hobbs, HH