Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Cheng S

PROVIDER: S-EPMC8379203 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Cheng Shiqiang S Wen Yan Y Liu Li L Cheng Bolun B Liang Chujun C Ye Jing J Chu Xiaomeng X Yao Yao Y Jia Yumeng Y Kafle Om Prakash OP Zhang Feng F

Translational psychiatry 20210820 1

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 exposu ...[more]

PMID: 34417442

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Project description:The role of gene-environment (GxE) interaction in disease and complex trait architectures is widely hypothesized, but currently unknown. Here, we apply three statistical approaches to quantify and distinguish three different types of GxE interaction for a given trait and E variable. First, we detect locus-specific GxE interaction by testing for genetic correlation rg<1 across E bins. Second, we detect genome-wide effects of the E variable on genetic variance by leveraging polygenic risk scores (PRS) to test for significant PRSxE in a regression of phenotypes on PRS, E, and PRSxE, together with differences in SNP-heritability across E bins. Third, we detect genome-wide proportional amplification of genetic and environmental effects as a function of the E variable by testing for significant PRSxE with no differences in SNP-heritability across E bins. Simulations show that these approaches achieve high sensitivity and specificity in distinguishing these three GxE scenarios. We applied our framework to 33 UK Biobank traits (25 quantitative traits and 8 diseases; average N=325K) and 10 E variables spanning lifestyle, diet, and other environmental exposures. First, we identified 19 trait-E pairs with rg significantly < 1 (FDR<5%) (average rg=0.95); for example, white blood cell count had rg=0.95 (s.e. 0.01) between smokers and non-smokers. Second, we identified 28 trait-E pairs with significant PRSxE and significant SNP-heritability differences across E bins; for example, BMI had a significant PRSxE for physical activity (P=4.6e-5) with 5% larger SNP-heritability in the largest versus smallest quintiles of physical activity (P=7e-4). Third, we identified 15 trait-E pairs with significant PRSxE with no SNP-heritability differences across E bins; for example, waist-hip ratio adjusted for BMI had a significant PRSxE effect for time spent watching television (P=5e-3) with no SNP-heritability differences. Across the three scenarios, 8 of the trait-E pairs involved disease traits, whose interpretation is complicated by scale effects. Analyses using biological sex as the E variable produced additional significant findings in each of the three scenarios. Overall, we infer a significant contribution of GxE and GxSex effects to complex trait and disease variance.

Dataset Information

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

Publications

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

Similar Datasets

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