Genomic screen for loci associated with alcohol dependence in mission Indians
Genomic screen for loci associated with alcohol dependence in mission Indians
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DOI：
10.1002/ajmg.b.30057
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发表时间：
2004-08-15
影响因子：
2.8
通讯作者：
Wilhelmsen, KC
中科院分区：
文献类型：
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作者：
Ehlers, CL;Gilder, DA;Wilhelmsen, KC
酒精依赖是印第安人发病和死亡的主要原因，然而在这个种族群体中，潜在的生物学因素仍然是虚幻的。本研究的目的是绘制印度裔家庭中DSM-III-R酒精依赖和两种较窄的酒精相关表型的易感位点。每个参与者都提供了血液样本，并使用酒精中毒遗传半结构化评估（SSAGA）完成了一次访谈，该评估用于进行酒精依赖诊断和较窄的戒断表型，以及饮酒严重程度。测定了791组微卫星多态性的基因型。对二分型DSM-III-R表型的多点方差成分LOD评分分析显示，在任何染色体位置，LOD评分峰值均未超过2.0。在酒精使用严重表型上，4号和12号染色体的LOD评分峰值超过2，在戒断表型上，6号、15号和16号染色体的LOD评分峰值超过2。先前已经报道了与4号、15号和16号染色体相关的酒精相关表型的证据，而尚未报道与6号和12号染色体相关的证据。联合连锁和关联分析表明，酒精脱氢酶1B基因多态性是该人群4号染色体连锁结果的部分原因。这些结果证实了先前酒精中毒分离研究中强调的几个染色体区域的重要性，并进一步确定了基因组的新区域，这些区域可能是所评估的受限表型或该印第安人群体所特有的。(C) 2004 Wiley-Liss, Inc。
Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain illusive. This study's aims were to map susceptibility loci for DSM-III-R alcohol dependence and two narrower alcohol-related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM-III-R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians. (C) 2004 Wiley-Liss, Inc.