The following is a summary of “Circulating Inflammatory Cytokines and Female Reproductive Diseases: A Mendelian Randomization Analysis,” published in the December 2023 issue of Endocrinology by Lin, et al.
Numerous studies have suggested the involvement of inflammation in the development of female reproductive diseases. However, establishing causality has remained a challenge. For a study, researchers sought to investigate whether genetically determined circulating levels of cytokines are causally linked to female reproductive diseases, aiming to identify potential novel drug targets for these conditions.
Instrumental variables (IVs) for 47 circulating cytokines were derived from a genome-wide association study (GWAS) meta-analysis involving 31,112 European individuals. IVs were obtained from protein quantitative trait loci and expression quantitative trait loci near genes. Summary data for 9 female reproductive diseases were sourced from GWAS meta-analyses of the UK Biobank and FinnGen. Mendelian randomization (MR) using the Wald ratio or inverse variance–weighted approach was employed, with subsequent sensitivity analyses and colocalization analyses to assess MR assumptions. Statistical significance in MR analyses was set at a false discovery rate <0.05. Replication and phenome-wide association studies were conducted to validate and explore potential side effects.
The findings suggested that elevated levels of macrophage colony-stimulating factor (MCSF), growth-regulated oncogene-alpha (GROα), and soluble intercellular adhesion molecule-1 were associated with increased risks of endometriosis, female infertility, and pre-eclampsia, respectively. High platelet-derived growth factor-BB (PDGF-BB) levels were linked to a reduced risk of ovarian aging. Replication analyses supported the associations between GROα and female infertility and between MCSF and endometriosis.
Four correlated pairs were identified, suggesting potential protein drug targets. PDGF-BB emerged as a noteworthy drug target for ovarian aging and MCSF for endometriosis.
Source: academic.oup.com/jcem/article-abstract/108/12/3154/7205641?redirectedFrom=fulltext
