Causal relationships between DNA methylation、Golgi membrane proteins、endoplasmic reticulum aminopeptidase and abnormal spermatozoa: a two sample Mendelian randomization study

Abstract

Abstract To explore the causal relationship between DNA methylation, Golgi membrane protein, endoplasmic reticulum aminopeptidase, ADP-ribose pyrophosphatase, mitochondrialon abnormal spermatozoa by two-sample Mendelian randomization (TSMR) method.Genetic loci closely related to DNA methylation PhenoAge acceleration, Golgi membrane protein 1, endoplasmic reticulum aminopeptidase 1, endoplasmic reticulum aminopeptidase 2, ADP-ribose pyrophosphatase, mitochondrial were selected as instrumental variables, andTSMR was performed by the inverse variance weighted method, MREgger regression, and weighted median method respectively. Sensitivity analysis was conducted to evaluate the robustness of the MR results.IVW showed that the DNA methylation PhenoAge acceleration(OR = 1.12, 95% CI: 1.01–1.23), Golgi membrane protein 1(OR = 1.22, 95% CI: 1.04–1.44), and endoplasmic reticulum aminopeptidase 2(OR = 1.13, 95% CI: 1.04–1.24) were associated with an increased risk of abnormal spermatozoa. However, there was no evidence of the association between ADP-ribose pyrophosphatase, mitochondrial (IVW OR = 1.25, 95% CI: 0.95–1.63), endoplasmic reticulum aminopeptidase 1 (IVW OR = 1.01, 95% CI: 0.90–1.12) and abnormal spermatozoa. Sensitivity analysis detected little evidence of pleiotropy in the current study.There is a positive causal relationship between DNA methylation PhenoAge acceleration, Golgi membrane protein 1, and endoplasmic reticulum aminopeptidase 2 on abnormal spermatozoa.