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

Abstract Primary biliary cholangitis (PBC) has the potential to impact skeletal muscles through the muscle-liver axis, subsequently leading to sarcopenia. Our study aims to explore the complex and unclear genetic structures between them. We investigated the common genetic basis of PBC and sarcopenia using advanced statistical genetics methods and genome - wide association summary analysis. We employed global and local genetic correlation to achieve valuable insights into potential shared biological mechanisms. We identified risk single nucleotide polymorphisms (SNPs) and functionally annotated genomic multi-markers by conducting the whole-genome unified testing of molecular characteristics. Finally, the fine-mapping analysis was prioritized to emphasize the significant causal genes in every region. Our study has revealed noteworthy genomic associations, suggesting the intricate genetic interplay between PBC and sarcopenia. At the genomic level, we identified 17 unique bivariate regions among 88 trait pairs, including chr3q27.1 and chr2q32.2-q32.3. The analysis of GWAS pleiotropy across traits has discovered 82,136 SNPs. Among these, bivariate locus correlation analysis has identified 136 pleiotropic sites. Bayesian colocation has pinpointed 18 causal variants. Functional enrichment analysis highlighted putative pleiotropic genomic regions, including brain and spleen. Our study has identified pleiotropic genomic regions linking PBC and sarcopenia, providing effective strategies for the treatment of diseases.