阿尔茨海默病与年龄相关性黄斑变性的因果关系:一项孟德尔随机化研究OA

OBJECTIVE To investigate the potential causal association between Alzheimer´s disease(AD)and age-related macular degeneration(AMD)using a two-sample Mendelian randomization(MR)analysis.METHODS Summary statistics from genome-wide association studies(GWAS)for AD and dry/wet AMD were obtained from the IEU Open GWAS database.Single-nucleotide polymorphisms(SNP)were used as instrumental variables for causal inference in a two-sample MR analysis.The inverse variance weighted(IVW)method was employed to assess causal relationships between AD and wet/dry AMD.Supplementary analyses included MR-Egger regression,weighted median estimator(WME),heterogeneity testing,and sensitivity analyses.RESULTS(1)SNP selection:13 SNP were selected for AD(exposure),wet AMD and dry AMD.(2)AD and wet AMD:A statistically significant causal relationship was observed between AD and wet AMD[OR=0.883,95%CI(0.784,0.885),F=34.848,P=0.000].MR-Egger regression showed no horizontal pleiotropy(P>0.05).The negative slope in the scatter plot further supported a causal effect.(3)AD and dry AMD:A statistically significant causal relationship was observed between AD and dry AMD[OR=0.875,95%CI(0.828,0.925),F=22.563,P=0.000].MR-Egger regression indicated no horizontal pleiotropy(P>0.05),and the negative scatter plot slope confirmed causality.CONCLUSIONS This study suggests a potential causal link between AD and AMD.Given the high risk of blindness associated with AMD,understanding and controlling its risk factors,as well as elucidating shared pathogenic pathways between these diseases,will aid in prevention and treatment research.