Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design
Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design
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DOI：
10.1017/s0033291706007884
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发表时间：
2006-10-01
影响因子：
6.9
通讯作者：
Martin, Nicholas G.
中科院分区：
文献类型：
--
作者：
Knopik, Valerie S.;Heath, Andrew C.;Martin, Nicholas G.
背景酗酒者的孩子更有可能经历高风险的环境暴露，包括产前物质暴露，并且更有可能表现出外化问题[例如注意力缺陷多动障碍（ADHD）]。虽然有证据表明，遗传影响和产前尼古丁和/或酒精暴露在确定ADHD的风险中发挥单独的作用，但在确定与母亲酒精使用障碍（AUD）相关的遗传风险和产前风险因素在确定ADHD风险中发挥的联合作用方面却做得很少。采用双胞胎的子女设计，使用logistic回归模型分析来自高风险家庭（作为父母的AUD一致或不一致的女性单卵和双卵双胞胎）和对照家庭的诊断电话访谈数据。有AUD病史的双胞胎的后代，以及非AUD同卵双胞胎的后代，其同卵双胞胎患有AUD，比对照组的后代更有可能表现出ADHD。这种模式与母体AUD和ADHD后代风险增加之间相关性的遗传解释一致。调整产前吸烟，这仍然是显着的预测，并没有删除显着的遗传关联之间的母亲AUD和后代ADHD。虽然母亲在怀孕期间吸烟可能有助于母亲AUD和后代ADHD风险之间的关联，但显着遗传相关性的证据表明：（i）多效性遗传效应，一些影响AUD风险的基因也影响ADHD的易感性;或（ii）ADHD是AUD的直接风险因素。
Background. Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD.Method. Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models.Results. Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD.Conclusions. While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.