MOLECULAR GENETIC STUDIES ON ALCOHOLISM IN AMERICAN INDIANS--SOUTHWESTERN TRIBE

美洲印第安人西南部落酗酒的分子遗传学研究

• 批准号: 6288662
• 负责人: DAVID GOLDMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6288662
• 关键词: Native Americans; alcoholism /alcohol abuse; behavioral genetics; disease /disorder proneness /risk; family genetics; gene expression; genetic markers; genetic polymorphism; genotype; human genetic material tag; human population genetics; human tissue; linkage mapping

To identify alcoholism vulnerability and protective genes, we collected and tested for linkage and pattern of genetic transmission families from American Indian populations. Such populations are relatively homogeneous genetically and environmentally. This report addresses an American Indian tribe in which alcoholism is highly prevalent. A total of 582 subjects from a large family genealogy were psychiatrically interviewed (SADS-L), blind rated for diagnosis and genotyped. An analysis (J. Long) of the familiality of alcoholism revealed a significant increase in relative risk in first- degree relatives of alcoholics. In females, the risk was highest in first-degree relatives, still significant at the 3rd degree of genetic relationship and compatible with a heritability of about 40%. Binge drinking in American Indians was found to be a behavior which is not, as has been alleged, benign or beneficial, but associated with dramatic increases in problems in multiple domains: social, violence/lawlessness, work and medical. A whole autosome genetic linkage analysis on a subset of the sample utilized 517 short tandem repeat markers. By sib-pair analysis, strong evidence for linkage to alcohol dependence [DSM-III-R] was found near the chromosome 11p telomere [near the DRD4 dopamine receptor locus] and the centromeric region of chromosome 4p [near the GABA receptor cluster]. A more modest linkage signal was also detected on chromosome 4q [at the location of the alcohol dehydrogenase gene cluster]. Simulation analyses confirmed that these linkage signals were statistically highly significant. The 11p finding could, on a conservative basis, have been randomly expected in about one in six whole genome linkage analyses. The 11p linkage has been replicated in a second subset from the original population. - population research, rural health, neurosciences, health & behavior, molecular genetics, gene mapping (human)

为了确定酒精中毒的脆弱性和保护基因，我们收集和测试的连锁和模式的遗传传播的家庭从美洲印第安人的人口。这些种群在遗传和环境上相对同质。这篇报道是关于一个酗酒非常普遍的美洲印第安部落的。共有582名受试者从一个大的家族系谱精神病学采访（SADS-L），盲评定诊断和基因分型。一项对酗酒家族性的分析（J. Long）显示，酗酒者的一级亲属的相对风险显著增加。在女性中，一级亲属的风险最高，在三级遗传关系中仍然显着，遗传率约为40%。在美洲印第安人中，酗酒被发现是一种不像人们所说的那样是良性或有益的行为，但与多个领域的问题急剧增加有关：社会，暴力/无法无天，工作和医疗。一个完整的常染色体遗传连锁分析的一个子集的样品利用517个短串联重复标记。通过同胞对分析，在染色体11 p端粒附近[靠近DRD 4多巴胺受体位点]和染色体4p着丝粒区域[靠近GABA受体簇]发现了与酒精依赖[DSM-III-R]相关的强有力证据。在染色体4 q [乙醇脱氢酶基因簇的位置]上也检测到更温和的连锁信号。模拟分析证实，这些连锁信号是统计上高度显着的。在保守的基础上，11 p的发现可能是随机预期的，大约六分之一的全基因组连锁分析。11 p连锁已在来自原始群体的第二个子集中复制。- 人口研究、农村健康、神经科学、健康与行为、分子遗传学、基因图谱（人类）