Hettema John M, An Seon-Sook, van den Oord Edwin J C G, Neale Michael C, Kendler Kenneth S, Chen Xiangning
Departments of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA 23298-0126, USA.
Psychiatr Genet. 2013 Apr;23(2):56-60. doi: 10.1097/YPG.0b013e32835d7048.
Quantitative trait loci identified in animal models provide potential candidate susceptibility loci for human disorders. In this study, we investigated whether internalizing disorders (anxiety disorders, major depression, and neuroticism) were associated with a region on human chromosome 1 syntenic with a quantitative trait locus for rodent emotionality.
We genotyped 31 single-nucleotide polymorphisms in genes located on chromosome 1q31.2 in a two-stage association study of 1128 individuals chosen for a high or a low genetic risk for internalizing disorders from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.
None of the individual single-nucleotide polymorphisms showed consistent association across stages. A four-marker haplotype in the regulator of G-protein signaling 1 gene (RGS1) was significantly associated with decreased internalizing risk in both stages, whereas another showed a nominal association with a higher risk.
Our data suggest that markers in the RGS1 gene might be in linkage disequilibrium with a protective allele that reduces the risk of anxiety and depressive disorders.
在动物模型中鉴定出的数量性状基因座为人类疾病提供了潜在的候选易感基因座。在本研究中，我们调查内化障碍（焦虑症、重度抑郁症和神经质）是否与人类1号染色体上与啮齿动物情绪性数量性状基因座同线的一个区域相关。
在弗吉尼亚成人精神病和物质使用障碍双生子研究中，我们对1128名因内化障碍遗传风险高或低而入选的个体进行了两阶段关联研究，对位于1q31.2染色体上基因中的31个单核苷酸多态性进行了基因分型。
没有单个单核苷酸多态性在各阶段显示出一致的关联。G蛋白信号调节因子1基因（RGS1）中的一个四标记单倍型在两个阶段均与内化风险降低显著相关，而另一个则与较高风险存在名义上的关联。
我们的数据表明，RGS1基因中的标记可能与一个降低焦虑和抑郁症风险的保护性等位基因处于连锁不平衡状态。
