A genetic association between primary biliary cholangitis (PBC) and connective tissue diseases (CTDs) has been reported, according to findings from a two-sample Mendelian randomization (MR) analysis published in the journal PLoS One.
In individuals with PBC, the immune system provokes an attack by targeting and destroying epithelial cells that line the bile ducts. Patients with the disease experience chronic inflammation and scarring, with the liver being the main organ targeted in PBC. Multiple body systems may be impacted as well, however, including those involved in the development of arthritis, pulmonary hypertension, interstitial lung disease and nephritis.
Although observational studies have shown a link between PBC and CTDs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), and Sjögren’s syndrome (SS), the causal direction remains to be elucidated. The researchers sought to evaluate the causal association between PBC and CTDs, in an effort to enrich our knowledge of PBC that occurs with comorbid CTDs. It is hoped that the results will play a role in earlier screening/diagnosis, more accurate disease stratification, and preemptive treatment of patients with the disorders.
In the MR study, numerous single-nucleotide polymorphisms (SNPs) were utilized as the instrumental variables (IVs). The MR analysis assumed the following three key statements:
- IVs are strongly associated with exposure factors
- IVs are independent of any confounding factors
- The IVs that are selected do not have a direct association with the outcome variable
Read more about PBC signs and symptoms
The primary analysis technique was inverse variance weighting (IVW), which was supplemented by the utilization of four sensitivity analyses to evaluate the strength of the study findings.
Results of the study revealed that based on IVW, genetically predicted PBC significantly elevated the risk for SLE by 43%, the risk for RA by 12%, the risk for SS by 18% and the risk for SSc by 25%.
Further, there was no relationship reported between CTDs as an exposure and PBC. No significant horizontal pleiotrophy was observed between PBCs and CTDs. All of the SNPs underwent heterogeneity testing, with a random effects model utilized if any heterogeneity was present.
“To the best of our knowledge, this is the first study to [investigate] the genetic link between PBC and CTDs[,] and to report that PBC increases the risk [for] multiple CTDs,” the authors stated, “To further elucidate the link between PBCs and CTD genes, multicenter cohort studies should be conducted in the future, using the GWAS database with a larger sample size, and the similar pathogenesis of the two should be explored.”
