Exploring the Shared Genetic Basis of Age at Menopause and Osteoarthritis

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

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.

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.

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.