Linkage of an alcoholism-related severity phenotype to chromosome 16
Linkage of an alcoholism-related severity phenotype to chromosome 16
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DOI：
10.1111/j.1530-0277.1998.tb05913.x
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发表时间：
1998-12-01
期刊：
影响因子：
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通讯作者：
Begleiter, H
中科院分区：
文献类型：
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作者：
Foroud, T;Bucholz, KK;Begleiter, H
有大量证据表明，酒精中毒风险具有重要的遗传因素。在寻找导致这种风险的基因时，酒精依赖的诊断标准可能不是最佳表型；相反，创造更同质的表型将导致更同质的遗传病因学。从 105 个酗酒家族的 830 名个体中收集的酗酒遗传学半结构化评估项目被用于潜在类别分析，以识别更同质的酗酒相关表型。选择四类解决方案：1 类，未受影响组； 2级，轻度问题组； 3级，中度受影响组； 4级，重灾组。对于反映严重酒精依赖的项目，第 3 类和第 4 类具有比第 1 类和第 2 类更高的症状认可概率，并且将其组合起来以提供足够的兄弟姐妹对进行遗传连锁分析。对分布在整个基因组中的总共 291 个标记进行了基因分型，平均标记间距离为 14 cM。进行连锁分析以检测 3 类和 4 类（中度和重度受影响的酗酒者）的基因座，其中 88% 符合酒精中毒遗传学合作研究，>99% 符合 ICD-10 酒精依赖标准。发现 16 号染色体上标记 D16S675 附近的一个基因座的证据，其最大多点 lod 得分为 4.0。对 16 号染色体上其他标记的分析得出的杆得分为 3.2，缩小了关键区域，并将该基因置于 D16S475 和 D16S675 之间，间隔 15 cM。
There is substantial evidence for a significant genetic component to the risk for alcoholism In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four-class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD-10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a rod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.