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

为了确定酒精中毒的易感性和保护性基因，我们收集并测试了美洲印第安人群体的遗传传播家系的连锁和模式。这些种群在基因和环境上都是相对同质的。这份报告针对的是一个酗酒现象非常普遍的美国印第安人部落。对来自一个大家族的582名受试者进行了精神病学访谈(SADS-L)，对其进行盲人诊断和基因分型。(J.Long)对酗酒熟悉度的分析显示，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，三级亲属的风险仍然显著，遗传率约为40%。美国印第安人的狂饮被发现是一种行为，并不像所说的那样是良性的或有益的，但与社会、暴力/违法、工作和医疗等多个领域的问题急剧增加有关。对样本子集的整个常染色体遗传连锁分析利用了517个短串联重复标记。通过同胞对分析，在染色体11p端粒[靠近DRD4多巴胺受体位点]和染色体4p着丝粒区域[靠近GABA受体簇]附近发现了与酒精依赖连锁的有力证据[DSM-III-R]。在染色体4Q[酒精脱氢酶基因簇的位置]上也检测到了更温和的连锁信号。模拟分析证实，这些连锁信号在统计上具有极高的显著性。在保守的基础上，11P的发现可能在大约六分之一的全基因组连锁分析中是随机预期的。在原始群体的第二个子集中复制了11P连锁。-人口研究、农村卫生、神经科学、健康与行为、分子遗传学、基因图谱(人类)

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)