A systematic review and cross-database analysis of single nucleotide polymorphisms underlying hip morphology and osteoarthritis reveals shared mechanisms

Abstract

Objective

Understanding the mechanisms of hip disease, such as osteoarthritis (OA), is crucial to advance their treatment. Such hip diseases often involve specific morphological changes. Genetic variations, called single nucleotide polymorphisms (SNPs), influence various hip morphological parameters. This study investigated the biological relevance of SNPs correlated to hip morphology in genome-wide association studies (GWAS). The SNP-associated genes were compared to genes associated with OA in other joints, aiming to see if the same genes play a role in both hip development and the risk of OA in other lower limb joints.

Methodology

A systematic literature review was conducted to identify SNPs correlated with hip morphology, based on the Population, Intervention, Comparison, Outcome, and Study (PICOS) framework. Afterwards, Gene Ontology (GO) analysis was performed, using EnrichR, on the SNP-associated genes and compared with non-hip OA-associated genes, across different databases.

Results

Reviewing 49 GWAS identified 436 SNPs associated with hip joint morphology, encompassing variance in bone size, structure and shape. Among the SNP-associated genes, SOX9 plays a pivotal role in size, GDF5 impacts bone structure, and BMP7 affects shape. Overall, skeletal system development, regulation of cell differentiation, and chondrocyte differentiation emerged as crucial processes influencing hip morphology. Eighteen percent of GWAS-identified genes related to hip morphology were also associated with non-hip OA.

Conclusion

Our findings indicate the existence of multiple shared genetic mechanisms across hip morphology and OA, highlighting the necessity for more extensive research in this area, as in contrast to the hip, the genetic background on knee or foot morphology remains largely understudied.