Palo Alto Veterans Affairs Health Care System, 795 Willow Road, MC151-J, Menlo Park, California 94025-2539, USA.
J Stud Alcohol Drugs. 2010 Sep;71(5):652-63. doi: 10.15288/jsad.2010.71.652.
Not only are substance-use disorders and externalizing disorders frequently comorbid, they often co-occur in families across generations. The current study examined the role of genetic and environmental influences in the relationship between paternal histories of drug dependence or alcohol dependence and offspring conduct disorder using an offspring-of-twins design.
Participants were male twins (n = 1,774) from the Vietnam Era Twin Registry, their offspring (n = 1,917), and mothers of the offspring (n = 1,202). Twins had a history of drug dependence, alcohol dependence, or neither. Based on the father's and his co-twin's drug-dependence or alcohol-dependence history and zygosity, risk groups were constructed to reflect different levels of genetic and environmental risk that were then used to predict offspring conduct disorder.
After controlling for potentially confounding variables, the offspring of men with a history of drug dependence or alcohol dependence had significantly higher rates of conduct disorder, compared with offspring of men without this history. Offspring at higher genetic risk had higher rates of conduct disorder. High-risk offspring at lower environmental risk had lower rates of conduct disorder but only in the case of paternal drug-dependence risk. Lower environmental risk did not influence rates of offspring conduct disorder when the father had an alcohol-dependence history.
Genetic risk associated with both paternal drug-dependence and paternal alcohol-dependence histories predicted offspring conduct-disorder risk, but only risk associated with paternal drug-dependence history was mitigated by having a low-risk environment. These results demonstrated a significant gene-environment interaction effect.
物质使用障碍和外化障碍不仅经常共病,而且它们通常在代际的家庭中同时发生。本研究采用双生子后代设计,考察了父亲的药物依赖或酒精依赖史与后代品行障碍之间关系中遗传和环境因素的作用。
参与者为越南时代双胞胎登记处的男性双胞胎(n=1774)、他们的后代(n=1917)和后代的母亲(n=1202)。双胞胎有药物依赖、酒精依赖或两者都没有的病史。根据父亲及其同卵双胞胎的药物依赖或酒精依赖史和同卵性,构建了风险组,以反映不同水平的遗传和环境风险,然后用这些风险组来预测后代的品行障碍。
在控制了可能的混杂变量后,与没有这种病史的男性的后代相比,有药物依赖或酒精依赖病史的男性的后代品行障碍的发生率显著更高。遗传风险较高的后代品行障碍的发生率较高。遗传风险较高但环境风险较低的高危后代品行障碍的发生率较低,但仅在父亲有药物依赖风险的情况下。当父亲有酒精依赖史时,环境风险较低并不影响后代品行障碍的发生率。
与父亲的药物依赖和酒精依赖史相关的遗传风险预测了后代品行障碍的风险,但只有与父亲的药物依赖史相关的风险在环境风险较低时才会减轻。这些结果表明存在显著的基因-环境交互作用效应。