Association of birth weight, childhood obesity, and age at menarche with ovarian function: an integrated Mendelian randomization study and bioinformatics analysis

Objective Observational studies have shown that birth weight, childhood obesity and age at menarche are associated with ovarian function, but there is still some controversy. Methods We mainly uses the inverse variance weighted (IVW) method for analysis, conducting heterogeneity, horizontal pleiotropy and MR Steiger test to evaluate the robustness of the results and the strength of causal relationships. Finally, preliminary bioinformatics analysis was conducted to explore the underlying biological mechanisms. Results Causal associations were found between childhood obesity, age at menarche and ovarian function, with a positive association between childhood obesity and ovarian dysfunction and a negative association between age at menarche and ovarian function. A total of 10 hub genes were identified, which are interconnected in an interaction network and play a role in the synthesis and secretion of lipids and parathyroid hormone. Conclusions Our study genetically confirms the causal association between childhood obesity, age at menarche and ovarian function; childhood obesity increases the risk of primary ovarian failure, and the later the age at menarche, the lower the risk of ovarian failure, which may be related to alterations in metabolic pathways such as intracellular receptors-mediated alterations in lipids and hormones.