Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples
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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DOI：
10.1038/sj.mp.4001764
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发表时间：
2006-02-01
影响因子：
11
通讯作者：
Kelsoe, JR
中科院分区：
文献类型：
--
作者：
Greenwood, TA;Schork, NJ;Kelsoe, JR
多巴胺转运体（DAT）是兴奋剂的作用部位，人类DAT基因（DAT1）的变异与几种精神疾病的易感性有关，包括注意缺陷多动障碍（ADHD）和双相情感障碍。我们之前已经报道了双相情感障碍与DAT1 3'端的新snp的关联。我们现在报告在DAT1中鉴定了20个额外的snp，共63个变体。我们还报告了在第二个独立家庭样本中与双相情感障碍相关的证据。使用传播不平衡检验分析了50个和70个家族的两个独立样本中8个新发现的snp和14个先前发现的snp。八个新发现的snp中的两个，一个在内含子8中，一个在内含子13中，被发现与双相情感障碍中度相关，每个都在两个独立样本中的一个中。在5个相邻SNPs的滑动窗口中对所有22个SNPs组成的单倍型进行分析，发现两个样本中内含子7和8附近的区域存在关联（同一窗口的经验p值分别为0.002和0.001）。在我们之前的研究中观察到的基因单倍型块结构在这个样本中得到了更大的分辨率，允许在基因中间区分第三个单倍型块。总之，这些数据与DAT1中传递双相情感障碍易感性的多种变异的存在是一致的。
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.