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

作　　者：Xinyuan Ge Lu Zhang Maojie Liu Xiao Wang Xin Xu Yuqian Yan Chan Tian Juan Yang Yang Ding Chengxiao Yu Jing Lu Longfeng Jiang Qiang Wang Qun Zhang Ci Song 

机构地区：[1]Department of Epidemiology,China International Cooperation Center on Environment and Human Health,Center for Global Health,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu,China [2]The Dumont-UCLA Transplant Center,Division of Liver and Pancreas Transplantation,Department of Surgery,David Geffen School of Medicine at UCLA,Los Angeles,CA,USA [3]Department of Health Promotion Center,Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital,Nanjing,Jiangsu,China [4]Department of Infectious Disease,The First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu,China [5]Department of Clinical Science,Intervention and Technology(CLINTEC),Karolinska Institutet,Stockholm,Sweden [6]Changzhou Medical Center,Nanjing Medical University,Nanjing,Jiangsu,China [7]Research Units of Cohort Study on Cardiovascular Diseases and Cancers,Chinese Academy of Medical Sciences,Beijing,China [8]Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University,Nanjing,Jiangsu,China

出　　处：《Journal of Clinical and Translational Hepatology》2024年第6期562-570,共9页临床与转化肝病杂志（英文版）

基　　金：supported by the Jiangsu Province Capability Improvement Project through Science,Technology and Education(grant number:ZDXK202248,recipient:QZ);National Natural Science Foundation of China(grant number:82373654,recipient:CS);Science and Technology Young Scientific and Technological Talents Project of Jiangsu Province(grant number:2021-50,recipient:CS);Key project of Changzhou Medical Center,Nanjing Medical University(grant number:CZKYCMCM202210,recipient:CS);Chinese Academy of Medical Sciences(grant number:2019RU038,recipient:CS).

摘　　要：Background and Aims:Age-related mosaic chromosomal alterations(mCAs)detected from genotyping of blood-de-rived 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 poly-morphisms 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-es of cirrhosis,1,775 cases of compensated cirrhosis,and 1,706 cases of decompensated cirrhosis.Compared to non-carriers,individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis(hazard ratio(HR)1.42,95%confidence interval(CI)1.12-1.81).This risk was higher in patients with expanded cell fractions of mCAs(cell fractions≥10%vs.cell fractions<10%),especially for the risk of decompensated cirrhosis(HR 2.03[95%CI 1.09-3.78]vs.1.14[0.80-1.64]).In comparison to non-carriers of mCAs with low genetic risk,individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk(HR5.39[95%CI 2.41-12.07]).Conclusions:The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.

关 键 词：UK Biobank CIRRHOSIS Mosaic chromosomal alterations Polygenic risk score Genetic susceptibility Interaction effect 

分 类 号：R575.2[医药卫生—消化系统]