Dong Dameng, Saeed Saboor, Chen Rucheng, Chen An, Zheng Weijun
School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Brain Behav. 2024 Dec;14(12):e70124. doi: 10.1002/brb3.70124.
Epidemiological studies have established an association between early sexual intercourse and intentional self-harm. However, the causal mechanisms, particularly the role of mental health disorders, remain elusive.
In this Mendelian randomization (MR) study, we leveraged genome-wide association study data from multiple sources. Age at first sexual intercourse (AFSI) statistics were derived from the UK Biobank, encompassing up to 406,457 participants of European ancestry. Intentional self-harm (ISH) genome-wide association study (GWAS) data were obtained from the FinnGen Biobank, comprising 218,792 European-descent individuals. We investigated the causal relationship between AFSI and ISH and quantified the mediating effects of major depressive disorder (MDD; n = 173,005), schizophrenia (SCZ; n = 127,906), and attention deficit hyperactivity disorder (ADHD; n = 55,374). Both two-step and multivariable MR approaches were employed to estimate the mediation effects of these psychiatric disorders.
The F-statistics of all retained SNPs are over 10, indicating our study has no weak instrument bias. The odds ratio (OR) indicated that early sexual intercourse substantially increases the risk of ISH (IVW: OR = 0.60, 95% CI = 0.54-0.66, p < 0.05). Specifically, MDD was found to mediate 31% of this effect and SCZ 12%, collectively accounting for 46% of the total effect.
Early sexual intercourse is associated with an increased risk of intentional self-harm, potentially mediated by psychiatric disorders. These findings emphasize the need for mental health screening and early intervention in adolescents with early sexual debuts.
流行病学研究已证实过早发生性行为与故意自伤之间存在关联。然而，其因果机制，尤其是心理健康障碍的作用，仍不明确。
在这项孟德尔随机化（MR）研究中，我们利用了来自多个来源的全基因组关联研究数据。首次性行为年龄（AFSI）统计数据源自英国生物银行，涵盖多达406,457名欧洲血统参与者。故意自伤（ISH）的全基因组关联研究（GWAS）数据取自芬兰生物银行，包括218,792名欧洲血统个体。我们研究了AFSI与ISH之间的因果关系，并量化了重度抑郁症（MDD；n = 173,005）、精神分裂症（SCZ；n = 127,906）和注意力缺陷多动障碍（ADHD；n = 55,374）的中介效应。采用两步法和多变量MR方法来估计这些精神疾病的中介效应。
所有保留的单核苷酸多态性（SNP）的F统计量均超过10，表明我们的研究不存在弱工具变量偏差。优势比（OR）表明，过早发生性行为会大幅增加ISH的风险（逆方差加权法：OR = 0.60，95%置信区间 = 0.54 - 0.66，p < 0.05）。具体而言，发现MDD介导了这一效应的31%，SCZ介导了12%，两者合计占总效应的46%。
过早发生性行为与故意自伤风险增加有关，可能由精神疾病介导。这些发现强调了对过早开始性行为的青少年进行心理健康筛查和早期干预的必要性。
