Phenome-Wide Association Analysis Reveals Novel Links Between Genetically Determined Levels of Liver Enzymes and Disease Phenotypes

Overview

Journal Phenomics

Publisher Springer

Date 2023 Mar 20

PMID 36939802

Authors

Zhenqiu Liu

Chen Suo

Yanfeng Jiang

Renjia Zhao

TieJun Zhang

Li Jin

Xingdong Chen

Affiliations

Soon will be listed here.

Abstract

Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-021-00033-y.

Citing Articles

SPA: effectively controlling for sample relatedness in large-scale genome-wide association studies of longitudinal traits.

Xu H, Ma Y, Xu L, Li Y, Liu Y, Li Y Nat Commun. 2025; 16(1):1413.

PMID: 39915470 PMC: 11803118. DOI: 10.1038/s41467-025-56669-1.

Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence.

Zhu Y, Jiang M, Gu Z, Shang H, Tang C, Guo T Hum Genomics. 2024; 18(1):71.

PMID: 38915066 PMC: 11197171. DOI: 10.1186/s40246-024-00642-4.

Protein truncating variants in mitochondrial-related nuclear genes and the risk of chronic liver disease.

Yuan H, Liu Z, Chen M, Xu Q, Jiang Y, Zhang T BMC Med. 2024; 22(1):239.

PMID: 38862964 PMC: 11167739. DOI: 10.1186/s12916-024-03466-0.

Comparison of post-resection survival between hepatocellular carcinoma patients in BCLC stage A or B who experience tumor rupture and patients in BCLC stage C who do not.

Jia-Yong S, Hong-Liang W, Ding-Wen L, Qing-Qing C, Yu-Tong C, Jun-Shao T Heliyon. 2024; 10(5):e27355.

PMID: 38449598 PMC: 10915404. DOI: 10.1016/j.heliyon.2024.e27355.

Causal associations between liver enzymes and diabetic microvascular complications: A univariable and multivariable Mendelian randomization.

Li Y, Zhang Q PLoS One. 2024; 19(1):e0296894.

PMID: 38232082 PMC: 10793938. DOI: 10.1371/journal.pone.0296894.

References

Jacobs M, van Greevenbroek M, van der Kallen C, Ferreira I, Feskens E, Jansen E . The association between the metabolic syndrome and alanine amino transferase is mediated by insulin resistance via related metabolic intermediates (the Cohort on Diabetes and Atherosclerosis Maastricht [CODAM] study). Metabolism. 2010; 60(7):969-75. DOI: 10.1016/j.metabol.2010.09.006. View

Pingault J, OReilly P, Schoeler T, Ploubidis G, Rijsdijk F, Dudbridge F . Using genetic data to strengthen causal inference in observational research. Nat Rev Genet. 2018; 19(9):566-580. DOI: 10.1038/s41576-018-0020-3. View

Li X, Meng X, He Y, Spiliopoulou A, Timofeeva M, Wei W . Genetically determined serum urate levels and cardiovascular and other diseases in UK Biobank cohort: A phenome-wide mendelian randomization study. PLoS Med. 2019; 16(10):e1002937. PMC: 6799886. DOI: 10.1371/journal.pmed.1002937. View

Tang S, Zhang J, Mei T, Guo H, Wei X, Zhang W . Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis. BMC Cancer. 2019; 19(1):1128. PMC: 6868855. DOI: 10.1186/s12885-019-6173-4. View

Monami M, Bardini G, Lamanna C, Pala L, Cresci B, Francesconi P . Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study. Metabolism. 2008; 57(3):387-92. DOI: 10.1016/j.metabol.2007.10.015. View

Sookoian S, Pirola C . Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol. 2015; 21(3):711-25. PMC: 4299326. DOI: 10.3748/wjg.v21.i3.711. View

Chatterjee N, Shi J, Garcia-Closas M . Developing and evaluating polygenic risk prediction models for stratified disease prevention. Nat Rev Genet. 2016; 17(7):392-406. PMC: 6021129. DOI: 10.1038/nrg.2016.27. View

Wu W, Sun Z, Yu J, Meng Q, Wang M, Miao J . A clinical retrospective analysis of factors associated with apathetic hyperthyroidism. Pathobiology. 2010; 77(1):46-51. DOI: 10.1159/000272954. View

Lawrence Y, Steiner J . Laboratory Evaluation of the Liver. Vet Clin North Am Small Anim Pract. 2017; 47(3):539-553. DOI: 10.1016/j.cvsm.2016.11.005. View

10.

Burgess S, Thompson S . Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017; 32(5):377-389. PMC: 5506233. DOI: 10.1007/s10654-017-0255-x. View

11.

De Silva N, Borges M, Hingorani A, Engmann J, Shah T, Zhang X . Liver Function and Risk of Type 2 Diabetes: Bidirectional Mendelian Randomization Study. Diabetes. 2019; 68(8):1681-1691. PMC: 7011195. DOI: 10.2337/db18-1048. View

12.

Ruhl C, Everhart J . Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States. Gastroenterology. 2003; 124(7):1821-9. DOI: 10.1016/s0016-5085(03)00395-0. View

13.

Webber M, Krishnan A, Thomas N, Cheung B . Association between serum alkaline phosphatase and C-reactive protein in the United States National Health and Nutrition Examination Survey 2005-2006. Clin Chem Lab Med. 2009; 48(2):167-73. DOI: 10.1515/CCLM.2010.052. View

14.

Liu Y, Patman G, Leathart J, Piguet A, Burt A, Dufour J . Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014; 61(1):75-81. DOI: 10.1016/j.jhep.2014.02.030. View

15.

Kunutsor S, Apekey T, Van Hemelrijck M, Calori G, Perseghin G . Gamma glutamyltransferase, alanine aminotransferase and risk of cancer: systematic review and meta-analysis. Int J Cancer. 2014; 136(5):1162-70. DOI: 10.1002/ijc.29084. View

16.

Koehler E, Sanna D, Hansen B, Rooij F, Heeringa J, Hofman A . Serum liver enzymes are associated with all-cause mortality in an elderly population. Liver Int. 2013; 34(2):296-304. DOI: 10.1111/liv.12311. View

17.

Liu J, Au Yeung S, Lin S, Leung G, Schooling C . Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study. Sci Rep. 2016; 6:38813. PMC: 5171875. DOI: 10.1038/srep38813. View

18.

Choi K, Han K, Park S, Chung H, Kim N, Yoo H . Implication of liver enzymes on incident cardiovascular diseases and mortality: A nationwide population-based cohort study. Sci Rep. 2018; 8(1):3764. PMC: 5830612. DOI: 10.1038/s41598-018-19700-8. View

19.

Grant A, Burgess S . Pleiotropy robust methods for multivariable Mendelian randomization. Stat Med. 2021; 40(26):5813-5830. PMC: 7612169. DOI: 10.1002/sim.9156. View

20.

Liu Z, Que S, Xu J, Peng T . Alanine aminotransferase-old biomarker and new concept: a review. Int J Med Sci. 2014; 11(9):925-35. PMC: 4081315. DOI: 10.7150/ijms.8951. View