Multi-omics tests identify novel shared genetic mechanisms of primary biliary cholestasis and sarcopenia

Primary biliary cholangitis (PBC) may affect skeletal muscles through the muscle-liver axis, subsequently leading to sarcopenia. Our study aims to explore the unclear genetic relationships between PBC and sarcopenia. We investigated the shared genetic architecture of PBC and sarcopenia using advanced statistical genetics methods and genome-wide association summary data. We employed global and local genetic correlation to gain potential shared biological mechanisms. We identified risk single nucleotide polymorphisms (SNPs) and functionally annotated genomic multi-markers by conducting the unified test for molecular signatures. Finally, we prioritized fine-mapping analysis to emphasize the significant causal genes. Our study has identified significant genomic associations, suggesting the complex genetic interactions between PBC and sarcopenia. At the genomic level, we identified 17 unique bivariate regions among 88 trait pairs. In the bivariate locus analysis, we identified a total of 136 pleiotropic loci, with ASTN1, TGFB2, and ACP1 being particularly prominent. Functional enrichment analysis highlighted putative pleiotropic genomic regions, including brain and spleen. Furthermore, the identified pleiotropic loci demonstrate strong signal transduction in the cGMP-PKG signaling pathway. Our findings highlight shared genetic links and causal relationships between PBC and sarcopenia, offering novel insights into their genetic mechanisms.