A multivariate Mendelian randomization study of Parkinson’s disease and coronary heart disease on amyotrophic lateral sclerosis

Abstract

Objective: To investigate the causal relationship between Parkinson’s disease (PD) and coronary heart disease (CHD) on amyotrophic lateral sclerosis (ALS) using genetic methods, and to investigate whether PD and CHD are independent factors influencing ALS.

Method: This study is based on the summary statistics of genome-wide association studies in the IEU Open GWAS database, with PD and CHD as exposure and ALS as outcome. Single-factor Mendelian randomization analysis was used to explore the causal relationship between exposure and results, and sensitivity analysis was performed. We also examined whether there is a reverse causal relationship between exposure and outcome. Finally, multivariate Mendelian randomization analysis was used to explore whether exposure independently affected outcomes.

Result: Genetically predicted IVW results showed CHD ( ID=ieu-a-7; OR=1.018 ; 95%CI=1.004-1.043; P=0.015) and PD (ID=ieu-b-7; OR=1.025; 95%CI=1.012-1.038; P<0.001) had a significant causal relationship with ALS. Multivariate Mendelian randomization analysis showed that CHD and PD were independent risk factors for ALS (P<0.05).

Conclusion: Our Mendelian randomization results show that the increased risk of PD and CHD has a negative impact on ALS and there is a significant causal relationship, which may provide new insights into the pathogenesis and treatment of ALS.