Abstract Purpose:The 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. 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.

The authors have declared no competing interest.

This study did not receive any funding.

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