TY - JOUR
T1 - The effect of liver enzymes on body composition
T2 - A Mendelian randomization study
AU - Liu, Junxi
AU - Yeung, Shiu Lun Au
AU - Kwok, Man Ki
AU - Leung, June Yue Yan
AU - Hui, Lai Ling
AU - Leung, Gabriel Matthew
AU - Mary Schooling, C.
N1 - Funding Information:
This work is a substudy of the “Children of 1997” birth cohort which was initially supported by the Health Care and Promotion Fund, Health and Welfare Bureau, Government of the Hong Kong SAR [HCPF grant 216106] and reestablished in 2005 with support from the Health and Health Services Research Fund, Government of the Hong Kong SAR, [HHSRF grant 03040771]; the Research Fund for the Control of Infectious Diseases in Hong Kong, the Government of Hong Kong SAR [RFCID grant 04050172]; the University Research Committee Strategic Research Theme (SRT) of Public Health, the University of Hong Kong. The Biobank Clinical follow-up was partly supported by the WYNG Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank colleagues at the Student Health Service and Family Health Service of the Department of Health for their assistance and collaboration. They also thank late Dr. Connie O for coordinating the project and all the fieldwork for the initial study in 1997–1998.
Publisher Copyright:
© 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Background Higher alanine transaminase (ALT), indicating poor liver function, is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function affects muscle mass. To clarify, we assessed the associations of liver enzymes with muscle and fat mass observationally with two-sample MR as a validation. Methods In the population-representative “Children of 1997” birth cohort (n = 3,455), we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) at ~17.5 years with muscle mass and body fat percentage observationally. Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) were applied to fat-free and fat mass in the UK Biobank (n = ~331,000) to obtain unconfounded MR estimates. Results Observationally, ALT was positively associated with muscle mass (0.11 kg per IU/L, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15% per IU/L, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (-0.03 kg per IU/L, 95% CI -0.04 to -0.02) and fat percentage (-0.02% per IU/L, 95% CI -0.03 to -0.01). Using MR, ALT was inversely associated with fat-free mass (-0.41 kg per 100% in concentration, 95% CI -0.64 to -0.19) and fat mass (-0.58 kg per 100% in concentration, 95% CI -0.85 to -0.30). ALP and GGT were unclearly associated with fat-free mass or fat mass. Conclusion ALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.
AB - Background Higher alanine transaminase (ALT), indicating poor liver function, is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function affects muscle mass. To clarify, we assessed the associations of liver enzymes with muscle and fat mass observationally with two-sample MR as a validation. Methods In the population-representative “Children of 1997” birth cohort (n = 3,455), we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) at ~17.5 years with muscle mass and body fat percentage observationally. Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) were applied to fat-free and fat mass in the UK Biobank (n = ~331,000) to obtain unconfounded MR estimates. Results Observationally, ALT was positively associated with muscle mass (0.11 kg per IU/L, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15% per IU/L, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (-0.03 kg per IU/L, 95% CI -0.04 to -0.02) and fat percentage (-0.02% per IU/L, 95% CI -0.03 to -0.01). Using MR, ALT was inversely associated with fat-free mass (-0.41 kg per 100% in concentration, 95% CI -0.64 to -0.19) and fat mass (-0.58 kg per 100% in concentration, 95% CI -0.85 to -0.30). ALP and GGT were unclearly associated with fat-free mass or fat mass. Conclusion ALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.
UR - https://www.scopus.com/pages/publications/85079316984
U2 - 10.1371/journal.pone.0228737
DO - 10.1371/journal.pone.0228737
M3 - Journal article
C2 - 32045441
AN - SCOPUS:85079316984
SN - 1932-6203
VL - 15
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e0228737
ER -
