Causal analysis of uterine artery pulsatility index-related proteins and the risk of precocious puberty in girls: a Mendelian randomization study.

Objectives: Precocious puberty in girls is a condition marked by the early onset of secondary sexual characteristics, with vascular factors like uterine artery pulsatility index having been suggested as potential indicators.

Methods: We performed Mendelian randomization (MR) analysis using genetic instruments from large-scale genome-wide association studies (GWAS) datasets, including ebi-a-GCST008403, ukb-a-250, and ukb-b-11971, to evaluate the relationship between arterial stiffness and precocious puberty. Exposure and outcome data were sourced from the GWAS Catalog, eQTLGen, and the R11_E4_PREPUB dataset. The TwoSampleMR package was employed to assess causal relationships, with several MR methods applied, including inverse variance weighted, MR Egger, weighted median, and mode-based methods.

Results: Our analysis of arterial stiffness using ebi-a-GCST008403, ukb-a-250, and ukb-b-11971 datasets did not show a statistically significant causal relationship with precocious puberty. The IVW method showed an OR of 0.707 (p=0.885) for arterial stiffness, indicating no reliable association. The investigation into MMP2 also yielded non-significant results across all methods, with an OR of 0.778 (p=0.330) from the IVW method. However, the analysis of MMP9 revealed a significant association with precocious puberty, showing an OR of 3.89 (p=0.004) using the IVW method, and an OR of 3.96 (p=0.027) from the Weighted Median method, indicating a strong positive effect of MMP9 on precocious puberty risk.

Conclusions: Our findings suggest that while arterial stiffness and other MMPs do not have a significant causal role, MMP9 may significantly increase the risk of precocious puberty in girls.