autoimmune disorders and their shared pathogenic mechanisms.
Both T1D and AILDs, which include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), are immune-mediated conditions where the body’s defense system mistakenly targets its own tissues. Although observational studies had earlier indicated possible associations between T1D and liver-related autoimmune conditions, questions around whether these associations reflected true causal relationships remained unanswered.
To address this, the research team employed a bidirectional Mendelian randomization (MR) approach using large-scale genome-wide association study (GWAS) datasets. This genetic technique leverages inherited variants as proxies to evaluate causal effects while reducing confounding factors commonly seen in observational studies. The primary analysis was performed using inverse variance weighting, and the findings were cross-validated with multiple sensitivity tests, including MR-Egger, weighted median, MR-PRESSO, and colocalization analyses.
The authors emphasized that these findings refine current understanding of comorbidities in T1D. Clinicians managing patients with T1D may need to be more vigilant in screening for autoimmune hepatitis and primary biliary cholangitis, given the genetic evidence of elevated risk.
“The work highlights the importance of recognizing autoimmune clustering in patients with type 1 diabetes,” the researchers noted, adding that further mechanistic studies are necessary to dissect the molecular drivers of these associations. Future work involving multi-omics profiling and experimental models could pave the way for targeted prevention and management strategies.
"By establishing a causal genetic basis, this study moves beyond simple observational associations and provides actionable insights that could eventually influence clinical surveillance and patient care in autoimmune disorders," the researchers concluded.
Liang, C., Li, X., Yang, Y. et al. Genetic evidence for causal links between type 1 diabetes and autoimmune liver diseases. Diabetol Metab Syndr 17, 360 (2025). https://doi.org/10.1186/s13098-025-01928-w
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