Haber Jon R, Jacob Theodore, Heath Andrew C
Palo Alto Veterans Affairs Health Care System, Menlo Park, California, United States of America.
Twin Res Hum Genet. 2005 Apr;8(2):120-31. doi: 10.1375/1832427053738782.
Not only are alcoholism and externalizing disorders frequently comorbid, they often co-occur in families across generations; for example, paternal alcoholism predicts offspring conduct disorder just as it does offspring alcoholism. To clarify this relationship, the current study examined the 'common genes' hypothesis utilizing a children-of-twins research design. Participants were male monozygotic (MZ) and dizygotic (DZ) twins from the Vietnam Era Twin Registry who were concordant or discordant for alcohol dependence together with their offspring and the mothers of those offspring. All participants were conducted through a structured psychiatric interview. Offspring risk of conduct disorder was examined as a function of alcoholism genetic risk (due to paternal and co-twin alcohol dependence) and alcoholism environmental risk (due to being reared by a father with an alcohol dependence diagnosis). After controlling for potentially confounding variables, the offspring of alcohol-dependent fathers were significantly more likely to exhibit conduct disorder diagnoses than were offspring of nonalcohol-dependent fathers, thus indicating diagnostic crossover in generational family transmission. Comparing offspring at high genetic and high environmental risk with offspring at high genetic and low environmental risk indicated that genetic factors were most likely responsible for the alcoholism-conduct disorder association. The observed diagnostic crossover (from paternal alcoholism to offspring conduct disorder) across generations in the context of both high and low environmental risk (while genetic risk remained high) supported the common genes hypothesis.
酗酒和外化性障碍不仅经常共病，还常常在跨代家庭中同时出现；例如，父亲酗酒预示着后代患品行障碍的风险，就如同预示后代患酗酒问题的风险一样。为了阐明这种关系，当前的研究采用双胞胎后代研究设计检验了“共同基因”假说。参与者是来自越南战争时期双胞胎登记处的男性同卵（MZ）和异卵（DZ）双胞胎，他们对酒精依赖情况一致或不一致，以及他们的后代和这些后代的母亲。所有参与者都接受了结构化的精神病学访谈。将品行障碍的后代风险作为酒精中毒遗传风险（由于父亲和双胞胎共同酒精依赖）和酒精中毒环境风险（由于由患有酒精依赖诊断的父亲抚养）的函数进行检验。在控制了潜在的混杂变量后，与非酒精依赖父亲的后代相比，酒精依赖父亲的后代患品行障碍诊断的可能性显著更高，从而表明在代际家庭传播中存在诊断交叉。将高遗传和高环境风险的后代与高遗传和低环境风险的后代进行比较表明，遗传因素最有可能是酗酒与品行障碍关联的原因。在高环境风险和低环境风险（而遗传风险仍然很高）的背景下观察到的跨代诊断交叉（从父亲酗酒到后代品行障碍）支持了共同基因假说。
