{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T01:53:07Z","timestamp":1768269187161,"version":"3.49.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> 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.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> 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.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Leukocytes with longer telomeres may have a lower risk of developing cirrhosis [OR = 0.645 (0.524, 0.795), <jats:italic>p<\/jats:italic> = 3.977E-05] and a higher chance of developing benign liver tumors [OR = 3.087 (1.721, 5.539), <jats:italic>p<\/jats:italic> = 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.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> 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.<\/jats:p>","DOI":"10.3389\/fgene.2023.1164024","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T11:43:09Z","timestamp":1690803789000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Causal relationships between telomere length and liver disease: a Mendelian randomization study"],"prefix":"10.3389","volume":"14","author":[{"given":"Shuangjing","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengtao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1126\/science.aab3389","article-title":"Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection","volume":"350","author":"Blackburn","year":"2015","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/350569a0","article-title":"Structure and function of telomeres","volume":"350","author":"Blackburn","year":"1991","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1002\/sim.7221","article-title":"A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization","volume":"36","author":"Bowden","year":"2017","journal-title":"Stat. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur. J. Epidemiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int. J. Epidemiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet. Epidemiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/EDE.0000000000000559","article-title":"Sensitivity analyses for robust causal inference from mendelian randomization analyses with multiple genetic variants","volume":"28","author":"Burgess","year":"2017","journal-title":"Epidemiology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1002\/hep.24173","article-title":"Constitutional telomerase mutations are genetic risk factors for cirrhosis","volume":"53","author":"Calado","year":"2011","journal-title":"Hepatology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"6287","DOI":"10.3748\/wjg.v20.i20.6287","article-title":"Telomere and telomerase in chronic liver disease and hepatocarcinoma","volume":"20","author":"Carulli","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/s43587-021-00166-9","article-title":"Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank","volume":"2","author":"Codd","year":"2022","journal-title":"Nat. Aging"},{"key":"B12","doi-asserted-by":"publisher","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: Genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"k601","DOI":"10.1136\/bmj.k601","article-title":"Reading mendelian randomisation studies: A guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1056\/NEJMoa2300503","article-title":"Familial clonal hematopoiesis in a long telomere syndrome","volume":"388","author":"DeBoy","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"eaaz6876","DOI":"10.1126\/science.aaz6876","article-title":"Determinants of telomere length across human tissues","volume":"369","author":"Demanelis","year":"2020","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1002\/hep.24217","article-title":"Telomerase gene mutations are associated with cirrhosis formation","volume":"53","author":"Hartmann","year":"2011","journal-title":"Hepatology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1111\/liv.13886","article-title":"Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease-related advanced fibrosis","volume":"38","author":"Kim","year":"2018","journal-title":"Liver Int."},{"key":"B35","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1080\/00365513.2022.2059698","article-title":"Nonalcoholic fatty liver disease and its prognosis associates with shorter leucocyte telomeres in a 21-year follow-up study","volume":"82","author":"Korkiakoski","year":"2022","journal-title":"Scand. J. Clin. Lab. Invest."},{"key":"B19","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ejca.2017.02.017","article-title":"Quality measures of the population-based Finnish Cancer Registry indicate sound data quality for solid malignant tumours","volume":"77","author":"Leinonen","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.ajhg.2020.02.006","article-title":"Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length","volume":"106","author":"Li","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1007\/s00438-020-01752-z","article-title":"Causal associations of waist circumference and waist-to-hip ratio with type II diabetes mellitus: New evidence from mendelian randomization","volume":"296","author":"Li","year":"2021","journal-title":"Mol. Genet. Genomics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"4247","DOI":"10.1002\/cncr.26015","article-title":"Longer leukocyte telomere length predicts increased risk of Hepatitis B virus-related hepatocellular carcinoma: A case-control analysis","volume":"117","author":"Liu","year":"2011","journal-title":"Cancer"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1093\/carcin\/bgs098","article-title":"Leukocyte telomere length predicts overall survival in hepatocellular carcinoma treated with transarterial chemoembolization","volume":"33","author":"Liu","year":"2012","journal-title":"Carcinogenesis"},{"key":"B24","doi-asserted-by":"publisher","first-page":"6383","DOI":"10.1038\/s41467-020-19966-5","article-title":"The role of polygenic risk and susceptibility genes in breast cancer over the course of life","volume":"11","author":"Mars","year":"2020","journal-title":"Nat. Commun."},{"key":"B25","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/j.1474-9726.2009.00485.x","article-title":"The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancer","volume":"8","author":"Mirabello","year":"2009","journal-title":"Aging Cell."},{"key":"B26","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.atherosclerosis.2017.09.016","article-title":"Leukocyte telomere length and cardiovascular disease in african Americans: The jackson heart study","volume":"266","author":"Mwasongwe","year":"2017","journal-title":"Atherosclerosis"},{"key":"B27","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/hep4.1803","article-title":"Inverse association of telomere length with liver disease and mortality in the US population","volume":"6","author":"Rattan","year":"2022","journal-title":"Hepatol. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1002\/ijc.33211","article-title":"Leukocyte telomere length, cancer incidence and all-cause mortality among Chinese adults: Singapore Chinese health study","volume":"148","author":"Samavat","year":"2021","journal-title":"Int. J. Cancer"},{"key":"B29","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1001\/jamainternmed.2021.7804","article-title":"Association of telomere length with risk of disease and mortality","volume":"182","author":"Schneider","year":"2022","journal-title":"JAMA Intern Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: An open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"630186","DOI":"10.3389\/fgene.2020.630186","article-title":"Telomere length as a marker of biological age: State-of-the-Art, open issues, and future perspectives","volume":"11","author":"Vaiserman","year":"2020","journal-title":"Front. Genet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1111\/j.1478-3231.2012.02801.x","article-title":"Telomere length in circulating serum DNA as a novel non-invasive biomarker for cirrhosis: A nested case-control analysis","volume":"32","author":"Wan","year":"2012","journal-title":"Liver Int."},{"key":"B34","doi-asserted-by":"publisher","first-page":"8435178","DOI":"10.1155\/2017\/8435178","article-title":"Shorter leukocyte telomere length in relation to presumed nonalcoholic fatty liver disease in Mexican-American men in NHANES 1999-2002","volume":"2017","author":"Wojcicki","year":"2017","journal-title":"Int. J. Hepatol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"650988","DOI":"10.3389\/fendo.2021.650988","article-title":"Association between weight change and leukocyte telomere length in US. Adults","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Endocrinol. (Lausanne)"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1164024\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T11:43:17Z","timestamp":1690803797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1164024\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,31]]},"references-count":36,"alternative-id":["10.3389\/fgene.2023.1164024"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1164024","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,31]]},"article-number":"1164024"}}