Li James J, Savage Jeanne E, Kendler Kenneth S, Hickman Matthew, Mahedy Liam, Macleod John, Kaprio Jaakko, Rose Richard J, Dick Danielle M
Waisman Center, Department of Psychology, University of Wisconsin-Madison, Madison, Wisconsin.
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.
J Stud Alcohol Drugs. 2017 May;78(3):442-451. doi: 10.15288/jsad.2017.78.442.
Alcohol use problems are common during adolescence and can predict serious negative outcomes in adulthood, including substance dependence and psychopathology. The current study examines the notion that alcohol use problems are driven by polygenic influences and that genetic influences may indirectly affect alcohol use problems through multiple pathways of risk, including variations in personality.
We used a genome-wide approach to examine associations between genetic risk for alcohol use problems, personality dimensions, and adolescent alcohol use problems in two separate longitudinal population-based samples, the Finnish Twin Cohort (FinnTwin12) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were 1,035 young adults from FinnTwin12 and 3,160 adolescents from ALSPAC. Polygenic risk scores (PRS) were calculated for ALSPAC using genome-wide association results (on alcohol dependence symptoms as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) from FinnTwin12. A parallel multiple mediator model was tested to examine whether the association between PRS and alcohol use problems assessed at age 16 could be explained by variations in personality dimensions assessed at age 13, including sensation seeking and negative emotionality.
PRS were marginally predictive of age 16 alcohol use problems; this association was partially mediated by sensation seeking. Polygenic variation underlying risk for alcohol use problems may directly influence the effects of sensation seeking, which in turn influence the development of alcohol use problems in later adolescence.
These findings contribute to the increasing evidence regarding the salience of sensation seeking during early adolescence as a potential constituent in the risk pathway underlying the development of alcohol use problems.
饮酒问题在青少年时期很常见，并且可以预测成年后的严重负面后果，包括物质依赖和精神病理学问题。本研究探讨了饮酒问题由多基因影响驱动的观点，以及基因影响可能通过多种风险途径间接影响饮酒问题，包括人格差异。
我们采用全基因组方法，在两个独立的基于人群的纵向样本中，即芬兰双胞胎队列（FinnTwin12）和雅芳亲子纵向研究（ALSPAC），研究饮酒问题的遗传风险、人格维度与青少年饮酒问题之间的关联。参与者包括来自FinnTwin12的1035名年轻成年人和来自ALSPAC的3160名青少年。利用FinnTwin12的全基因组关联结果（基于《精神障碍诊断与统计手册》第四版定义的酒精依赖症状）为ALSPAC计算多基因风险评分（PRS）。测试了一个平行多重中介模型，以检验13岁时评估的人格维度差异（包括寻求刺激和消极情绪）是否可以解释PRS与16岁时评估的饮酒问题之间的关联。
PRS对16岁时的饮酒问题有微弱的预测作用；这种关联部分由寻求刺激介导。饮酒问题风险背后的多基因变异可能直接影响寻求刺激的作用，进而影响青少年后期饮酒问题的发展。
这些发现为越来越多的证据提供了补充，即青春期早期寻求刺激作为饮酒问题发展潜在风险途径的一个组成部分具有重要意义。
