基于英国人群GWAS数据的孟德尔随机化研究:性行为特征与脑出血及缺血性卒中风险的因果关系分析OA

Objective:To investigate the potential causal relationship between age at first sexual intercourse(AFSI)and lifetime number of sexual partners(LNSP)and the risk of intracerebral haemorrhage(ICH)and ischemic stroke(IS)using a Mendelian randomisation approach.Method:This study systematically investigates the potential causal relationship between AFSI and LNSP and ICH,IS and its subtypes,using pooled genome-wide association study(GWAS)data from the UK Biobank.Single nucleotide polymorphisms(SNPs)that were significantly associated with the exposure were selected as instrumental variables through rigorous screening criteria,ensuring that they satisfied the fundamental assumptions of Mendelian randomisation(MR):correlation,independence,and exclusion restriction.Causal effects were primarily estimated using inverse variance weighting(IVW)and supplemented with weighted median estimation and MR-Egger regression analysis to assess robustness and potential horizontal pleiotropy bias.Furthermore,Bayesian weighted MR and reverse MR analyses validated the directionality,robustness,and reliability of the causal inferences.Result:A Mendelian randomisation analysis revealed that the AFSI was significantly and negatively associated with the overall risk of intracranial haemorrhage.This association was stronger for deep intracranial haemorrhage and lobar intracerebral haemorrhage.Furthermore,AFSI was significantly associated with a reduced risk of ischaemic stroke and its major subtypes,including stroke due to small vessel disease,large artery atherosclerosis,and cardioembolism.The LNSP was negatively associated with the risk of deep intracerebral haemorrhage and lobar haemorrhage,while being positively associated with the risk of cerebellar haemorrhage.Conclusion:Among European populations,MR suggests a potential causal link between AFSI and the risk of hemorrhagic and ischemic stroke.Meanwhile,LNSP correlates with specific stroke subtypes.These findings provide genetic evidence that supports causal inferences linking characteristics of sexual behaviour to stroke risk.