Association of Mosaic Chromosomal Alterations and Genetic Factors with the Risk of Cirrhosis

Abstract

Background and Aims: Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction. Methods: mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk. Results: Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cas