Family-based association of FKBP5 in bipolar disorder
Family-based association of FKBP5 in bipolar disorder
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DOI：
10.1038/sj.mp.4002141
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发表时间：
2009-03-01
影响因子：
11
通讯作者：
Potash, J. B.
中科院分区：
文献类型：
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作者：
Willour, V. L.;Chen, H.;Potash, J. B.
FKBP5基因产物与糖皮质激素受体形成复合物的一部分，并可调节皮质醇结合亲和力。该基因的变异与抑郁症复发的增加和抗抑郁治疗的快速反应有关。我们试图确定常见的FKBP5变异是否会导致双相情感障碍。我们对317个家庭的554名双相子女进行了FKBP5的7个标签单核苷酸多态性（SNPs）基因分型，加上两个以前与疾病相关的SNPs，主要来自两项研究。单标记和单倍型分析进行了FBAT和EATDT采用标准的双极表型。还使用11个疾病相关变量作为协变量进行关联分析。在加性遗传模型下，rs4713902表现出主等位基因的显著过度传递（P=0.0001），这在两个样本集之间是一致的（P=0.004和0.006）。rs7757037在显性模型下显示出最强的关联证据（P=0.001）。这一结果在两个数据集之间是一致的（P=0.017和0.019）。主导模型产生了适度的关联证据（P
The FKBP5 gene product forms part of a complex with the glucocorticoid receptor and can modulate cortisol-binding affinity. Variations in the gene have been associated with increased recurrence of depression and with rapid response to antidepressant treatment. We sought to determine whether common FKBP5 variants confer risk for bipolar disorder. We genotyped seven tag single-nucleotide polymorphisms (SNPs) in FKBP5, plus two SNPs previously associated with illness, in 317 families with 554 bipolar offspring, derived primarily from two studies. Single marker and haplotypic analyses were carried out with FBAT and EATDT employing the standard bipolar phenotype. Association analyses were also conducted using 11 disease-related variables as covariates. Under an additive genetic model, rs4713902 showed significant overtransmission of the major allele (P=0.0001), which was consistent across the two sample sets (P=0.004 and 0.006). rs7757037 showed evidence of association that was strongest under the dominant model (P=0.001). This result was consistent across the two datasets (P=0.017 and 0.019). The dominant model yielded modest evidence for association (P