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A Mendelian Randomization Study Identifies the Causal Association between Plasma Mitochondrial CHCHD Proteins and Polycystic Ovary Syndrome

Shiyang Wei, Yafeng Wang, Niping Liu, Renfeng Zhao

Purpose: The objective of this research was to examine the causal link between Polycystic Ovary Syndrome (PCOS) and plasma mitochondrial Coiled-Coil-Helix-Coiled-Coil-Helix Domain (CHCHD) proteins using a Mendelian Randomization (MR) method

Methods: We 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.

Results: The 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).

Conclusion: Our 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.

A 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.