Ontology highlight
ABSTRACT: Background
While extensive research highlighted the involvement of metabolism and immune cells in female reproductive diseases, causality remains unestablished.Methods
Instrumental variables for 486 circulating metabolites (N = 7824) and 731 immunophenotypes (N = 3757) were derived from a genome-wide association study (GWAS) meta-analysis. FinnGen contributed data on 14 female reproductive disorders. A bidirectional two-sample Mendelian randomization study was performed to determine the relationships between exposures and outcomes. The robustness of results, potential heterogeneity, and horizontal pleiotropy were examined through sensitivity analysis.Results
High levels of mannose were found to be causally associated with increased risks of gestational diabetes (GDM) (OR [95% CI], 6.02 [2.85-12.73], p = 2.55 × 10-6). A genetically predicted elevation in the relative count of circulating CD28-CD25++CD8+ T cells was causally related to increased female infertility risk (OR [95% CI], 1.26 [1.14-1.40], p = 1.07 × 10-5), whereas a high absolute count of NKT cells reduced the risk of ectopic pregnancy (OR [95% CI], 0.87 [0.82-0.93], p = 5.94 × 10-6). These results remained consistent in sensitivity analyses.Conclusions
Our study supports mannose as a promising GDM biomarker and intervention target by integrating metabolomics and genomics.
SUBMITTER: Shen HH
PROVIDER: S-EPMC10813709 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Shen Hui-Hui HH Zhang Yang-Yang YY Wang Xuan-Yu XY Wang Cheng-Jie CJ Wang Ying Y Ye Jiang-Feng JF Li Ming-Qing MQ
Biomolecules 20240116 1
<h4>Background</h4>While extensive research highlighted the involvement of metabolism and immune cells in female reproductive diseases, causality remains unestablished.<h4>Methods</h4>Instrumental variables for 486 circulating metabolites (<i>N</i> = 7824) and 731 immunophenotypes (<i>N</i> = 3757) were derived from a genome-wide association study (GWAS) meta-analysis. FinnGen contributed data on 14 female reproductive disorders. A bidirectional two-sample Mendelian randomization study was perfo ...[more]