Gilligan S B, Reich T, Cloninger C R
Graduate Division of Biological and Biomedical Sciences, Washington University, St. Louis, Missouri.
Genet Epidemiol. 1987;4(6):395-414. doi: 10.1002/gepi.1370040602.
Etiologic heterogeneity in alcohol abuse was evaluated in 195 extended pedigrees, comprising 288 nuclear families of 140 male and 55 female Caucasian American hospitalized alcoholics. Previous adoption studies in Sweden demonstrated differential heritability of two patterns of alcohol abuse in men: type-2 alcoholism exhibited early onset of abuse associated with criminal behavior, while type-1 abuse began at a later age, uncomplicated by antisocial traits. Alcohol abuse in female Swedish adoptees was relatively homogeneous and similar to the late-onset, type-1 abuse. The notion of etiologic heterogeneity, as suggested by the Stockholm Adoption Studies, was examined in the American pedigrees by contrasting the models of familial transmission of susceptibility to alcoholism obtained via segregation analyses of families of male versus female probands. Families of male probands demonstrated significant familial resemblance, accounted for by a multifactorial-polygenic background in addition to a major (gene) effect. In contrast, familial resemblance in the pedigrees of female probands was attributed solely to a multifactorial-polygenic effect. We considered whether some families of male alcoholics were similar to families of female probands, who expressed type-1 abuse predominantly. Pedigrees of male probands were separated in two groups: (1) "female-like" families had a better likelihood for the model obtained for families of female probands than the one for families of all male probands, (2) "male-like" families had a better likelihood for the model of familial transmission describing families of all male probands. A statistically significant difference in the pattern of familial transmission was observed between the "male-like" and "female-like" groups. Discriminant function analysis of alcohol-related symptoms showed that the familial subtypes differed in clinical features as well. Alcohol abuse by male relatives in "male-like" families was characterized by the early onset of inability to abstain entirely from alcohol or lack of desire to stop drinking; in contrast, abuse in "female-like" families was characterized by late onset of guilt feelings and loss of control over binge drinking.
在195个扩展家系中评估了酒精滥用的病因异质性，这些家系包括288个核心家庭，其中有140名美国白人男性和55名美国白人女性住院酗酒者。瑞典之前的收养研究表明，男性中两种酒精滥用模式的遗传度存在差异：2型酒精中毒表现为与犯罪行为相关的早期滥用，而1型滥用开始于较晚年龄，且无反社会特征。瑞典女性收养者中的酒精滥用相对同质，类似于晚发性1型滥用。正如斯德哥尔摩收养研究所表明的病因异质性概念，在美国家系中通过对比男性与女性先证者家庭的酒精中毒易感性家族传递模型进行了检验。男性先证者家庭表现出显著的家族相似性，除了主要（基因）效应外，还由多因素-多基因背景所解释。相比之下，女性先证者家系中的家族相似性仅归因于多因素-多基因效应。我们考虑了一些男性酗酒者家庭是否与主要表现为1型滥用的女性先证者家庭相似。男性先证者的家系被分为两组：（1）“女性样”家庭对于女性先证者家庭所获得的模型比所有男性先证者家庭的模型有更好的拟合度；（2）“男性样”家庭对于描述所有男性先证者家庭的家族传递模型有更好的拟合度。在“男性样”和“女性样”组之间观察到家族传递模式存在统计学上的显著差异。对与酒精相关症状的判别函数分析表明，家族亚型在临床特征上也有所不同。“男性样”家庭中男性亲属的酒精滥用特征是早期出现完全无法戒酒或缺乏戒酒意愿；相比之下，“女性样”家庭中的滥用特征是后期出现内疚感和对暴饮失去控制。
