Novel Genetic Variants Identified for Knee Osteoarthritis in South Indian Population

Knee Osteoarthritis (kOA), the most prevalent form of arthritis, poses a significant global health challenge, contributing substantially to disability. Its complex origins involve both genetic predispositions and environmental influences. While extensive research has illuminated the genetic landscape of kOA in European and East Asian populations, the specific genetic underpinnings in South Indian communities have remained largely unexplored.

To address this knowledge gap, researchers conducted whole-exome sequencing on clinically diagnosed kOA patients and healthy controls of South Indian origin. Through systematic processing and refinement using nine in silico prediction tools, the study successfully identified seven rare, putatively pathogenic genetic variants. These key variants were found in genes such as COL11A1, HTRA1, PLEC, RAPH1, SOX9, ATP7B, and PXN. Significantly, these genes converge in pathways central to extracellular matrix organization, collagen fibril assembly, and cell junction organization, processes essential for cartilage integrity.

Importantly, these identified variants are absent from existing clinical variant databases and genome-wide association datasets of European and East Asian ancestry. This strongly suggests population-specific contributions to disease susceptibility within the South Indian population. As lead author Vijetha notes in the paper, "The findings underscore the importance of extending genomic studies to underrepresented groups, with implications for understanding population-specific genetic risk factors in osteoarthritis."