Short telomeres, but not accelerated epigenetic or proteomic age, increase fibrotic lung disease risk: Mendelian randomisation with pleiotropy dissection and independent replication

What To Know

This preprint used Mendelian randomisation to test whether measures of biological ageing (several DNA methylation “clocks,” proteomic age, and leukocyte telomere length) causally influence risk of immune-related diseases including interstitial lung disease (ILD)/idiopathic pulmonary fibrosis (IPF), Crohn’s disease and ulcerative colitis.

The main, replicated finding reported is that shorter genetically predicted telomere length increases risk of fibrotic lung disease (strongest for clinically defined IPF), and this effect remained after excluding known telomere-maintenance loci.

The study did not find evidence that epigenetic clocks or proteomic age acceleration causally affect the tested immune diseases, though the authors note the analyses could only exclude moderate-to-large effects for those measures.

The authors also performed a range of sensitivity and pleiotropy checks and attempted replication in independent IPF case collections. The article is a preprint (abstract-level structured content here), so it has not completed peer review.

The methods are genetic inference (Mendelian randomisation) rather than interventional trials, which supports causal inference from genetic variation but does not substitute for clinical studies.