Endophenotypes successfully lead to gene identification: Results from the collaborative study on the genetics of alcoholism
Endophenotypes successfully lead to gene identification: Results from the collaborative study on the genetics of alcoholism
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DOI：
10.1007/s10519-005-9001-3
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发表时间：
2006-01-01
影响因子：
2.6
通讯作者：
Begleiter, H
中科院分区：
文献类型：
--
作者：
Dick, DM;Jones, K;Begleiter, H
已经提出使用内表型作为一种策略来帮助复杂表型的基因鉴定工作[Gottesman，I.一、Shields J.（1972）.精神分裂症与遗传学：一项双胞胎研究Vantage Point。伦敦：学术界]。作为酒精中毒遗传学合作研究（COGA）项目的一部分，我们分析了电生理学内表型，除了临床诊断，作为我们努力确定参与酒精依赖易感性的基因的一部分。在本文中，我们总结了来自两个染色体区域的连锁和关联分析的公开结果，其中使用内表型已经成功地导致鉴定与酒精依赖相关的基因[GABRA 2（Edenberg et al.，（2004年）。Am. J.哈姆。Genet. 74：705-714）和CHRM 2（Wang等人，（2004年）。Hum.摩尔Genet. 13：1903-1911）]。我们在COGA项目中的经验是，内表型分析提供了几个诊断表型的优势，包括连锁信号的强度和定位。我们的研究结果提供了一个成功的使用endophenotypes来识别基因参与易感性复杂的精神病表型，最初提出的Gottesman和盾牌在1972年的策略。
The use of endophenotypes has been proposed as a strategy to aid gene identification efforts for complex phenotypes [Gottesman, I. I., and Shields J. (1972). Schizophrenia and Genetics: A Twin Study Vantage Point. London: Academic]. As part of the Collaborative Study of the Genetics of Alcoholism (COGA) project, we have analyzed electrophysiological endophenotypes, in addition to clinical diagnoses, as part of our effort to identify genes involved in the predisposition to alcohol dependence. In this paper we summarize published results from linkage and association analyses of two chromosomal regions in which the use of endophenotypes has successfully led to the identification of genes associated with alcohol dependence [GABRA2 (Edenberg et al., (2004). Am. J. Hum. Genet. 74:705-714) and CHRM2 (Wang et al., (2004). Hum. Mol. Genet. 13:1903-1911)]. Our experience in the COGA project has been that the analysis of endophenotypes provides several advantages over diagnostic phenotypes, including the strength and localization of the linkage signal. Our results provide an illustration of the successful use of endophenotypes to identify genes involved in the predisposition to a complex psychiatric phenotype, a strategy originally proposed by Gottesman and Shields in 1972.