Exploring the Shared Genetic Basis of Age at Menopause and Osteoarthritis.

Abstract

Objective: The relationship between age at menopause and osteoarthritis (OA) remains unclear.

Methods: The genetic commonalities between age at menopause and OA were investigated using data from publicly accessible genome-wide association studies. A variety of methods were employed in this exploration, such as linkage disequilibrium score regression (LDSC), high-definition likelihood, LAVA, pleiotropic analysis under composite null hypothesis, and summary-databased Mendelian randomization. Additionally, causal relationships were probed through the application of Mendelian randomization techniques.

Results: A significant negative genetic correlation was identified between age at menopause and OA, with a genetic correlation coefficient of -0.115 and a P value of 1.79 × 10^-6, as determined by LDSC. Then, a number of single nucleotide polymorphisms associated with both OA and the age at menopause were identified to exhibit pleiotropic effects. Age at menopause had a causal effect on OA. In addition, six potentially functional genes, C7orf73, RP11-148O21.2, BLK, PAM16, MAPK3, and DBF4B, have been identified to exhibit associations with both age at menopause and OA.

Conclusion: This study's results provide a deeper comprehension of the genetic underpinnings and complex interplay between age at menopause and OA. It contributes novel perspectives for the discovery of shared genetic-based therapeutic targets, highlighting the value of understanding their common genetic framework for developing future treatments.