A Mendelian randomization study identifies the causal association between plasma mitochondrial CHCHD proteins and polycystic ovary syndrome

Abstract

PurposeThe objective of this research was to examine the causal link between PCOS and plasma mitochondrial coiled-coil-helix-coiled-coil-helix domain(CHCHD) proteins using a Mendelian randomization (MR) method. MethodsWe performed a two-sample MR analyses by utilizing summary statistics obtained from genome-wide association studies (GWAS) of PCOS (642 cases and 118,228 controls) and the levels of CHCHD2 and CHCHD10 in plasma (3,301 individuals). The inverse-variance weighted (IVW) method was used for the MR analyses, along with additional sensitivity analyses. ResultsThe association between CHCHD2 and an increased risk of PCOS was identified (OR = 1.682; 95% CI = (1.231, 2.297); P = 0.001). The discovery of CHCHD10 revealed a protective impact on the likelihood of PCOS (OR = 0.828, 95% CI= 0.698-0.981, p = 0.029). The MR results were confirmed to be robust through the analysis of heterogeneity (P > 0.05) and pleiotropy (P > 0.05). ConclusionOur findings indicates that mitochondrial proteins CHCHD2 and CHCHD10 may play an important role in the pathogenesis of PCOS. Additional research is necessary to clarify the underlying mechanisms and investigate the potential of these proteins as targets for therapeutic intervention in PCOS. What does this study add to the clinical workA strong causal relationship has been established between two plasma mitochondrial complexes with coiled-coil-helix domains and polycystic ovary syndrome. The exact role of serum mitochondrial protein in polycystic ovary syndrome needs to be investigated via large-scale randomization trials or further studies.