People with primary biliary cholangitis (PBC) may face a greater risk of muscle loss, known as sarcopenia, due to shared genetic factors that connect liver and muscle health, according to a study published recently in Scientific Reports.
This new study found significant overlap in genes linked to both conditions, suggesting that inflammation or metabolic changes in the liver may directly affect skeletal muscle function.
“Our findings reveal the shared genetic pleiotropic loci and potential causal relationships between PBC and sarcopenia,” stated this study’s authors. They continued, “These insights highlight the biological connections underlying their phenotypic associations and provide novel perspectives on the genetic mechanisms of PBC-sarcopenia comorbidity.”
Using large-scale genetic data, researchers analyzed the shared genetic architecture of PBC and sarcopenia through advanced statistical methods. They discovered 17 key genomic regions among 88 studied trait pairs, identifying 136 shared genetic sites, called pleiotropic loci, where the same genes may influence both diseases. Prominent genes included ASTN1, TGFB2 and ACP1, all known to play roles in cell signaling and tissue maintenance.
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Several of the shared genes were most active in the brain and spleen, tissues that help regulate metabolism, immunity and muscle coordination. This study also found that many of these genes are involved in the cGMP–PKG signaling pathway, which helps control blood flow, muscle tone and bile metabolism. Disruptions in this pathway could contribute to both liver scarring and muscle weakness.
The strongest genetic link appeared in a region on chromosome 3 (3q27.1), involving the genes KLHL24, MAP6D1 and AP2M1. Another highly associated region, on chromosome 2 (2q32.2–q32.3), included genes tied to immune system regulation and cell energy production. These findings were supported by multiple independent analyses, strengthening confidence in the results.
The researchers also identified specific genetic variants, such as rs2272593 in NFKBIL1 and rs9275219 in HLA-DQB1, that were associated with both liver inflammation and muscle decline. In total, more than 82,000 shared genetic risk markers were detected across analyses, providing a detailed map of how the two conditions may interact at the molecular level.
For patients, these results suggest that PBC may not only damage bile ducts but also contribute to physical weakness and reduced muscle mass. Understanding the muscle-liver genetic link could lead to more comprehensive care strategies and future therapies targeting both liver function and muscle preservation.
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