Importance: Large consortia of genome wide association studies have yielded more accurate polygenic risk scores (PRS) that aggregate the small effects of many genetic variants to characterize the genetic architecture of disorders and provide a personalized measure of genetic risk. Objective: We examined whether a PRS for smoking measured genetic risk for general behavioral disinhibition by estimating its associations with externalizing and internalizing psychopathology and related personality traits. We examined these associations at multiple time points in adolescence using more refined phenotypes defined by stable characteristics across time and at young ages, which reduced potential confounds associated with cumulative exposure to substances and reverse causality. Methods: Random intercept panel models were fit to symptoms of conduct disorder, oppositional defiant disorder, major depressive disorder (MDD), and teacher ratings of externalizing and internalizing problems and personality traits at ages 11, 14, and 17 years-old in the Minnesota Twin Family Study (N = 3225). Results: The smoking PRS had strong associations with the random intercept factors for all the externalizing measures (mean standardized ꞵ = .27), agreeableness (ꞵ=-.22, 95% CI: -.28, -.16), and conscientiousness (ꞵ=-.19, 95% CI: -.24, -.13), but was not significantly associated with the internalizing measures (mean ꞵ = .06) or extraversion (ꞵ=.01, 95% CI: -.05, .07). After controlling for smoking at age 17, the associations with the externalizing measures (mean ꞵ = .13) and personality traits related to behavioral control (mean ꞵ = -.10) remained statistically significant. Conclusions and Relevance: The smoking PRS measures genetic influences that contribute to a spectrum of phenotypes related to behavioral disinhibition including externalizing psychopathology and normal-range personality traits related to behavioral control, but not internalizing psychopathology. Continuing to identify the correlates and delineate the mechanisms of the genetic influences associated with disinhibition could have substantial impact in mitigating a variety of public health problems (e.g., mental health, academic achievement, criminality).

中文翻译：

---

吸烟的多基因风险评分与心理病理学和人格特质的外在化有关，但与青春期的心理病学内在化无关

重要性：大型的全基因组关联研究协会已得出更准确的多基因风险评分（PRS），该评分汇总了许多遗传变异的微小影响，以表征疾病的遗传结构并提供了个性化的遗传风险度量。目的：我们研究了吸烟的PRS是否通过评估其与外部和内在化的心理病理学及相关人格特征的关联来测量一般行为抑制的遗传风险。我们使用更精细的表型在青春期的多个时间点检查了这些关联，这些表型由不同时期和年轻时期的稳定特征定义，从而减少了与物质累积暴露和反向因果关系相关的潜在混淆。方法：随机截取面板模型适合行为障碍的症状，在明尼苏达州双胞胎家庭研究（N = 3225）中，对立反抗性障碍，重度抑郁症（MDD）以及11岁，14岁和17岁时对内在化和内在化问题以及人格特质的教师评分。结果：吸烟PRS与所有外部化措施（平均标准化standardized = .27），可喜程度（ꞵ=-。22、95％CI：-。28，-。16）和尽责性均与随机拦截因子密切相关。 （ꞵ=-。19，95％CI：-。24，-。13），但与内部化指标（平均值ꞵ= .06）或外向性（ꞵ= .01，95％CI ：-）没有显着相关。 05，.07）。在控制了17岁的吸烟后，与外在化措施（平均ꞵ= .13）和与行为控制相关的人格特质的关联（平均ꞵ= -.10）仍然具有统计学意义。结论和相关性：吸烟PRS测量的遗传影响可导致一系列与行为抑制相关的表型，包括外在的心理病理学和与行为控制有关的正常范围的人格特质，而不是内在的心理病理学。继续确定与禁忌症相关的遗传因素的相关性和机制，可能对减轻各种公共卫生问题（例如心理健康，学业成就，犯罪）具有重大影响。