Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.
BMC Psychiatry. 2023 Apr 7;23(1):237. doi: 10.1186/s12888-023-04720-0.
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.
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.
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), and self-harm (OR = 1.12; 95% CI, 1.01-1.24; P = 2.90 × 10). GWEIS revealed multiple suggestive genes interacted with birth by CS for anxiety, such as DKK2 (rs13137764, P = 1.24 × 10, adjusted P = 2.68 × 10) and ATXN1 (rs62389045, P = 4.38 × 10, adjusted P = 3.55 × 10). For self-harm, significant gene-environment interactions of birth by CS on self-harm were detected, such as ALDH1A2 (rs77828167, P = 1.62 × 10; rs116899929, P = 1.92 × 10) and DAB1 (rs116124269, P = 3.20 × 10; rs191070006, P = 3.63 × 10).
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.
人们很少关注剖宫产（CS）对成人焦虑和自伤风险的潜在遗传机制。
利用英国生物库队列，首先采用逻辑回归模型评估成人焦虑和自伤与 CS 的关联。然后使用 CS 作为暴露变量，通过 PLINK2.0 进行全基因组与环境相互作用研究（GWEIS），以确定与 CS 相关的焦虑和自伤的相互作用基因。
在观察性研究中，CS 与焦虑（比值比（OR）= 1.24；95%置信区间（CI），1.12-1.38；P = 4.86×10）和自伤（OR = 1.12；95%CI，1.01-1.24；P = 2.90×10）之间存在显著关联。GWEIS 显示，多个与 CS 相互作用的候选基因与焦虑相关，如 DKK2（rs13137764，P = 1.24×10，调整后 P = 2.68×10）和 ATXN1（rs62389045，P = 4.38×10，调整后 P = 3.55×10）。对于自伤，CS 对自伤的基因-环境相互作用有显著影响，如 ALDH1A2（rs77828167，P = 1.62×10；rs116899929，P = 1.92×10）和 DAB1（rs116124269，P = 3.20×10；rs191070006，P = 3.63×10）。
我们的研究结果表明 CS 与成人焦虑和自伤的风险相关。我们还发现一些与 CS 相互作用的基因可能会影响焦虑和自伤的风险，这可能为这些精神障碍的发病机制提供新的线索。
