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首页> 外文期刊>Molecular Psychiatry >Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples
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Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples

机译：人多巴胺转运蛋白基因中其他变体的鉴定为两个独立样本中的双相情感障碍相关提供了进一步的证据

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The dopamine transporter (DAT) is the site of action of stimulants, and variations in the human DAT gene (DAT1) have been associated with susceptibility to several psychiatric disorders including attention deficit hyperactivity disorder (ADHD) and bipolar disorder. We have previously reported the association of bipolar disorder to novel SNPs in the 3' end of DAT1. We now report the identification of 20 additional SNPs in DAT1 for a total of 63 variants. We also report evidence for association to bipolar disorder in a second independent sample of families. Eight newly identified SNPs and 14 previously identified SNPs were analyzed in two independent samples of 50 and 70 families each using the transmission disequilibrium test. Two of the eight new SNPs, one in intron 8 and one in intron 13, were found to be moderately associated with bipolar disorder, each in one of the two independent samples. Analysis of haplotypes comprised of all 22 SNPs in sliding windows of five adjacent SNPs revealed an association to the region near introns 7 and 8 in both samples (empirical P-values 0.002 and 0.001, respectively, for the same window). The haplotype block structure observed in the gene in our previous study was confirmed in this sample with greater resolution allowing for discrimination of a third haplotype block in the middle of the gene. Together, these data are consistent with the presence of multiple variants in DAT1 that convey susceptibility to bipolar disorder.
机译：多巴胺转运蛋白（DAT）是刺激物的作用部位，人DAT基因（DAT1）的变异与多种精神疾病的易感性有关，包括注意力缺陷多动障碍（ADHD）和躁郁症。我们以前曾报道过双相情感障碍与DAT1的3'端新型SNP的关联。我们现在报告鉴定出DAT1中另外20个SNP，共63个变体。我们还在第二个独立的家庭样本中报告了与躁郁症相关的证据。使用传输不平衡测试，分别在50个和70个科的两个独立样本中分析了8个新发现的SNP和14个先前发现的SNP。在两个独立样本之一中，发现八个新SNP中的两个，一个在内含子8中，一个在内含子13中，与躁郁症有中度相关性。在五个相邻SNP的滑动窗口中对所有22个SNP进行的单倍型分析表明，两个样品均与内含子7和8内含子附近区域相关（同一窗口的经验P值分别为0.002和0.001）。在我们先前的研究中，在该基因中观察到的单倍型嵌段结构在此样品中得到了证实，具有更高的分辨率，从而可以区分基因中间的第三个单倍型嵌段。总之，这些数据与DAT1中多种变异的存在一致，这些变异传达了对躁郁症的易感性。

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