Abstract
BACKGROUND: Limited efforts have been paid to explore the underlying genetic mechanisms of birth by caesarian section (CS) affecting the risks of adult anxiety and self-harm. METHODS: Using UK Biobank cohort, the logistic regression model was first applied to evaluate the associations of adult anxiety and self-harm with birth by CS. Using birth by CS as exposure variables, genome-wide by environment interaction study (GWEIS) was then applied by PLINK2.0 to identify associated genes interacting with birth by CS for anxiety and self-harm. RESULTS: In the observational study, significant associations were observed between birth by CS and anxiety (odds ratio (OR) = 1.24; 95% confidence interval (CI), 1.12-1.38; P = 4.86 × 10(- 5)), and self-harm (OR = 1.12; 95% CI, 1.01-1.24; P = 2.90 × 10(- 2)). GWEIS revealed multiple suggestive genes interacted with birth by CS for anxiety, such as DKK2 (rs13137764, P = 1.24 × 10(- 9), adjusted P = 2.68 × 10(- 7)) and ATXN1 (rs62389045, P = 4.38 × 10(- 8), adjusted P = 3.55 × 10(- 6)). For self-harm, significant gene-environment interactions of birth by CS on self-harm were detected, such as ALDH1A2 (rs77828167, P = 1.62 × 10(- 8); rs116899929, P = 1.92 × 10(- 8)) and DAB1 (rs116124269, P = 3.20 × 10(- 8); rs191070006, P = 3.63 × 10(- 8)). CONCLUSIONS: Our results suggested that birth by CS was associated with the risk of adult anxiety and self-harm. We also discovered some genes interacted with birth by CS might influence the risk of anxiety and self-harm, which may provide novel clues for the pathogenesis of those mental disorders.