Schuckit M A, Edenberg H J, Kalmijn J, Flury L, Smith T L, Reich T, Bierut L, Goate A, Foroud T
Department of Psychiatry, University of California, San Diego 92161-2002, USA.
Alcohol Clin Exp Res. 2001 Mar;25(3):323-9.
The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified.
A 12-item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair analyses were carried out for the SRE measure related to early drinking experiences.
Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores > or = 2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample.
These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.
人类和动物对酒精的低反应水平（LR）都受遗传影响，低LR是酗酒者后代的一个特征，据报道它可预测10年和15年后的酗酒情况。导致低LR的基因尚未被确定。
来自酒精中毒遗传学协作研究（COGA）的745名个体填写了一份测量LR的12项问卷，即酒精效应自评（SRE）工具，这些个体都有可用的遗传物质。使用336个标记对这些受试者进行基因分型，这些标记的平均杂合度为0.74，平均标记间距为10.5厘摩。对与早期饮酒经历相关的SRE测量进行了定量和定性非参数同胞对分析。
相关个体间SRE分数的相关性显著，大多数值在0.16至0.22之间，而无关个体间的相关性不显著，为0.03或更低。使用前5个变量（首次饮酒的前5次）进行的连锁分析确定了4个对数优势分数≥2.0的染色体区域，其最大值也靠近一个标记。这些染色体区域之一先前在COGA样本中与酒精依赖有关。
这些数据证明了用SRE测量的对酒精低LR的家族性本质，并提示了几个可能导致该现象的染色体区域。
