Ma Jennie Z, Zhang Dong, Dupont Randolph T, Dockter Michael, Elston Robert C, Li Ming D
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S104. doi: 10.1186/1471-2156-4-S1-S104.
There is substantial evidence for a significant genetic component to the risk for alcoholism. However, susceptibility loci or genes for alcohol dependence remain largely unknown. To identify susceptibility loci for alcohol dependence, we selected 329 extended families from the Framingham Heart Study population in which at least one family member reported alcohol consumption during the interview in 1970-1971, and performed genome-wide linkage analyses using various analytical methods.
Multi-point sib-pair regression analysis using the SIBPAL program of S.A.G.E. provided strong evidence for linkage of alcohol dependence to chromosomes 9 (p-value < 0.0001) and weak evidence to chromosomes 15 and 16 (p-value < 0.005). To confirm these findings, we re-analyzed the same data set by various methods implemented in GENEHUNTER and found that only one region was significant with a LOD score > 2.0 by the variance-component method. This region is located on chromosome 9 between markers GATA21F05 and GATA81C04.
Analyses of the Framingham Heart Study population provided evidence of genetic susceptibility loci for alcohol dependence on chromosomes 9, 15, and 16. The genomic region identified on chromosome 9 was particularly interesting because the region has also been previously reported to be linked to alcohol dependence in the American Indian population by another group.
有大量证据表明酒精成瘾风险存在显著的遗传因素。然而,酒精依赖的易感基因座或基因仍 largely 未知。为了确定酒精依赖的易感基因座,我们从弗雷明汉心脏研究人群中选取了 329 个大家庭,其中至少有一名家庭成员在 1970 - 1971 年的访谈中报告有饮酒行为,并使用各种分析方法进行全基因组连锁分析。
使用 S.A.G.E. 的 SIBPAL 程序进行的多点同胞对回归分析为酒精依赖与 9 号染色体的连锁提供了有力证据(p 值 < 0.0001),与 15 号和 16 号染色体的连锁提供了微弱证据(p 值 < 0.005)。为了证实这些发现,我们通过 GENEHUNTER 中实现的各种方法重新分析了同一数据集,发现只有一个区域通过方差成分法的 LOD 得分 > 2.0 具有显著性。该区域位于 9 号染色体上标记 GATA21F05 和 GATA81C04 之间。
对弗雷明汉心脏研究人群的分析为 9 号、15 号和 16 号染色体上酒精依赖的遗传易感基因座提供了证据。在 9 号染色体上确定的基因组区域特别有趣,因为此前另一组研究也曾报道该区域与美洲印第安人群中的酒精依赖有关。