Causal relationships between telomere length and liver disease: a Mendelian randomization study

Front Genet. 2023 Jul 31:14:1164024. doi: 10.3389/fgene.2023.1164024. eCollection 2023.

Abstract

Background: Leukocyte telomere length and hepatic disorders have been linked in various research studies, although their causative association has not been clarified. This study investigated the causal relationship between the length of telomeres on peripheral blood leukocytes and certain liver disorders. Methods: Mendelian randomization (MR) analysis was used to examine the relationship between leukocyte telomere length and risk of liver disease using the publicly accessible worldwide gene-wide association study (GWAS) database. The weighted mode, weighted median, and inverse variance weighted (IVW) methods were employed as supplements to the IVW approach, which is the main analytical method. Results: Leukocytes with longer telomeres may have a lower risk of developing cirrhosis [OR = 0.645 (0.524, 0.795), p = 3.977E-05] and a higher chance of developing benign liver tumors [OR = 3.087 (1.721, 5.539), p = 1.567E-04]. There was no direct link between telomere length and fatty liver, hepatic fibrosis, or liver cancer. Our findings in the replication analysis agreed with those of the previous studies. Conclusion: Further research is needed to examine the mechanisms underlying the probable causal association between the length of leukocyte telomeres and cirrhosis and benign liver cancer.

Keywords: Mendelian randomization; cirrhosis; liver; single-nucleotide polymorphisms; telomere.