Multi-omics and molecular testing: A new insight into the genetic mechanisms of sarcopenia and arthritis

Sarcopenia and arthritis, characterized by age-related progressive loss of skeletal muscle mass and function, profoundly impact the well-being of older adults. Our study endeavors to explore the unclear genetic structure between them. Using advanced statistical genetic approaches and genome-wide association study (GWAS) summary statistics, we explored the shared genetic basis among multiple manifestations of sarcopenia and four distinct arthritic conditions: osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and gouty arthritis. A local analysis method for variant annotation was applied to approximately 2,495 genomic regions of equal size and partial independence, determining binary local genetic correlations among these regions. Cross-phenotype association GWAS studies have revealed many genetic variations associated with complex traits. Transcriptome-wide association studies were conducted using weights from various human tissues to identify risk loci. We functionally annotated genomic multi-markers and fine-mapping colocalization by conducting the whole-genome unified testing of molecular characteristics. Significant correlations between sarcopenia and four types of arthritis were detected through comprehensive and local genetic correlation analyses. At the genomic level, we identified 19 unique bivariate regions, including chr3q27.3, chr5q35.3, and chr12q13.2-q13.3, involving multiple human cell lines such as KBM7, GM12878, and IMR90. Gene enrichment analyses revealed that the selected loci primarily signaled through elementary pathways, including central nervous system neuron axonogenesis, glutamatergic synapse, and beta-catenin binding. Specifically, GDF5 and DNAJC27 were prioritized as the most probable candidate genes via precision transcriptomics. Our study has identified pleiotropic genomic regions linking sarcopenia and arthritis, providing effective strategies for the treatment of diseases.