背景:为了确定重度抑郁症(MD)和酒精使用障碍(AUD)的遗传风险因素是否与有效的压力源-配偶死亡相互作用,父母,和兄弟姐妹-在预测事件中,分别,MD和AUD。
方法:MD和AUD注册从瑞典国家注册管理机构进行评估。在1960-1970年瑞典出生的个体中,我们确定了7586、388459和34370,分别,配偶,父母,和兄弟姐妹。我们从18岁或2002年开始随访,2018年结束随访。我们检查了事件发生时间-6个月内的MD注册或一年内的AUD-以添加剂量表,使用Nelson-Aalen估计器。遗传风险通过家庭遗传风险评分(FGRS)进行评估。
结果:在控制配偶死亡的主要影响的单独模型中,父母,和兄弟姐妹,FGRS,和性,在随后的MD登记预测中,在MD遗传风险与亲属死亡之间的所有分析中都发现了显著的交互作用.类似的结果模式,尽管相互作用效应较弱,观察到AUD的遗传风险和AUD注册风险。双相情感障碍(BD)和焦虑症(AD)的遗传风险也与事件暴露在预测MD中相互作用。
结论:MD和AUD的遗传风险部分通过增加个体对环境应激源的致病作用的敏感性起作用。对于MD的预测,对于AD和BD的遗传风险也观察到类似的影响。
BACKGROUND: To determine whether genetic risk factors for major depression (MD) and alcohol use disorder (AUD) interact with a potent stressor - death of spouse, parent, and sibling - in predicting episodes of, respectively, MD and AUD.
METHODS: MD and AUD registrations were assessed from national Swedish registries. In individuals born in Sweden 1960-1970, we identified 7586, 388 459, and 34 370 with the loss of, respectively, a spouse, parent, and sibling. We started following subjects at age 18 or the year 2002 with end of follow-up in 2018. We examined time to event - a registration for MD within 6 months or AUD within a year - on an additive scale, using the Nelson-Aalen estimator. Genetic risk was assessed by the Family Genetic Risk Score (FGRS).
RESULTS: In separate models controlling for the main effects of death of spouse, parent, and sibling, FGRS, and sex, significant interactions were seen in all analyses between genetic risk for MD and death of relative in prediction of subsequent MD registration. A similar pattern of results, albeit with weaker interaction effects, was seen for genetic risk for AUD and risk for AUD registration. Genetic risk for bipolar disorder (BD) and anxiety disorders (AD) also interacted with event exposure in predicting MD.
CONCLUSIONS: Genetic risk for both MD and AUD act in part by increasing the sensitivity of individuals to the pathogenic effects of environmental stressors. For prediction of MD, similar effects are also seen for genetic risk for AD and BD.