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

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.

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.

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).

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. What does this study add to the clinical work 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors