Traumatic events during childhood and its risks to substance use in adulthood: an observational and genome-wide by environment interaction study in UK Biobank.

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.