Multi-Omics Data Reveal Causal Associations Of Cellular Senescence-Related Genes In Rheumatoid Arthritis: A Summary-Data-Based Mendelian Randomization And Co-Localization Analysis
Rheumatoid arthritis (RA) is a complex autoimmune disease that causes chronic inflammation in the joints. Recent research has highlighted the role of cellular senescence, a process where cells stop dividing but remain active, in the development of RA. This study utilized a powerful approach combining various types of biological data, known as multi-omics data, to investigate the causal relationships between genes involved in cellular senescence and RA.
Researchers employed advanced statistical methods, including Mendelian randomization and co-localization analysis, to determine if specific genetic variations that influence cellular senescence also directly impact the risk of RA. Mendelian randomization uses genetic variations as natural experiments to infer causal links, helping to overcome limitations of traditional observational studies. Co-localization analysis further confirmed that the observed genetic associations for both cellular senescence traits and RA risk likely share the same underlying genetic cause.
Through this comprehensive analysis, five key genes—BCL2L1, DNMT3B, ERRFI1, NEK4, and RAF1—were identified as having significant causal associations with RA. For instance, specific genetic modifications (methylation variations) in the BCL2L1 gene were found to be negatively associated with RA risk, potentially by increasing the gene’s activity. Conversely, certain genetic variations in the RAF1 gene were linked to an increased risk of RA, also through their effect on gene expression.
These findings provide crucial insights into the genetic mechanisms by which cellular aging processes contribute to RA. Understanding these causal links could pave the way for developing new diagnostic tools and targeted therapies for rheumatoid arthritis by focusing on these specific genes and the pathways of cellular senescence.
Source: link to paper