We aimed to explore the underlying genetic mechanisms of traumatic events during childhood affecting the risks of adult substance use in present study. Using UK Biobank cohort, linear regression model was first applied to assess the relationships between cigarette smoking and alcohol drinking in adults with traumatic events during childhood, including felt hated by family member (41,648–111,465), felt loved (46,394–124,481) and sexually molested (47,598–127,766). Using traumatic events as exposure variables, genome-wide by environment interaction study was then performed by PLINK 2.0 to identify cigarette smoking and alcohol drinking associated genes interacting with traumatic events during childhood. We found that the frequency of cigarette smoking was significantly associated with felt hated by family member (coefficient = 0.42, P < 1.0 × 10^–9), felt loved (coefficient = −0.31, P < 1.0 × 10^–9) and sexually molested (coefficient = 0.46, P < 1.0 × 10^–9). We also observed weaker associations of alcohol drinking with felt hated by family member (coefficient = 0.08, P = 3.10 × 10^–6) and felt loved (coefficient = −0.06, P = 3.15 × 10^–7). GWEIS identified multiple candidate loci interacting with traumatic events, such as CTNNA3 (rs189142060, P = 4.23 × 10^–8) between felt hated by family member and the frequency of cigarette smoking, GABRG3 (rs117020886, P = 2.77 × 10^–8) between felt hated by family member and the frequency of alcohol drinking. Our results suggested the significant impact of traumatic events during childhood on the risk of cigarette smoking and alcohol drinking.

我们旨在探索儿童时期创伤事件影响本研究中成人物质使用风险的潜在遗传机制。使用 UK Biobank 队列，线性回归模型首次应用于评估在儿童期遭受创伤事件的成年人吸烟和饮酒之间的关系，包括感到被家庭成员憎恨 (41,648–111,465)、感到被爱 (46,394–124,481) 和性行为。骚扰（47,598–127,766）。使用创伤事件作为暴露变量，然后由 PLINK 2.0 进行全基因组环境相互作用研究，以确定与儿童时期创伤事件相互作用的吸烟和饮酒相关基因。我们发现吸烟的频率与家人讨厌的感觉显着相关（系数 = 0.42，P  < 1.0 × 10 ^–9），感到被爱（系数 = -0.31，P  < 1.0 × 10 ^–9）和性骚扰（系数 = 0.46，P  < 1.0 × 10 ^–9）。我们还观察到饮酒与家人讨厌（系数 = 0.08，P  = 3.10 × 10 ^–6）和被爱（系数 = -0.06，P  = 3.15 × 10 ^–7）之间的关联较弱。GWEIS 确定了多个与创伤事件相互作用的候选基因座，例如 CTNNA3 (rs189142060, P  = 4.23 × 10 ^–8 ) 与家庭成员的厌恶感和吸烟频率之间的关系，GABRG3 (rs117020886, P = 2.77 × 10 ^–8 ) 感到被家人讨厌和饮酒频率之间。我们的研究结果表明，童年时期的创伤事件对吸烟和饮酒的风险有显着影响。