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Article: The effect of liver enzymes on body composition: A Mendelian randomization study
Title | The effect of liver enzymes on body composition: A Mendelian randomization study |
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Authors | |
Editors | Editor(s):Meyre, D |
Keywords | Fats Cohort studies Genome-wide association studies Diabetes mellitus Hand strength |
Issue Date | 2020 |
Publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action |
Citation | PLoS One, 2020, v. 15 n. 2, p. article no. e0228737 How to Cite? |
Abstract | 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. |
Persistent Identifier | http://hdl.handle.net/10722/281156 |
ISSN | 2021 Impact Factor: 3.752 2020 SCImago Journal Rankings: 0.990 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | LIU, J | - |
dc.contributor.author | Au Yeung, SL | - |
dc.contributor.author | Kwok, MK | - |
dc.contributor.author | Leung, YYJ | - |
dc.contributor.author | Hui, LL | - |
dc.contributor.author | Leung, GM | - |
dc.contributor.author | Schooling, CM | - |
dc.contributor.editor | Meyre, D | - |
dc.date.accessioned | 2020-03-09T09:50:56Z | - |
dc.date.available | 2020-03-09T09:50:56Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | PLoS One, 2020, v. 15 n. 2, p. article no. e0228737 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/10722/281156 | - |
dc.description.abstract | 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. | - |
dc.language | eng | - |
dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | - |
dc.relation.ispartof | PLoS ONE | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Fats | - |
dc.subject | Cohort studies | - |
dc.subject | Genome-wide association studies | - |
dc.subject | Diabetes mellitus | - |
dc.subject | Hand strength | - |
dc.title | The effect of liver enzymes on body composition: A Mendelian randomization study | - |
dc.type | Article | - |
dc.identifier.email | Au Yeung, SL: ayslryan@hku.hk | - |
dc.identifier.email | Kwok, MK: maggiek@hku.hk | - |
dc.identifier.email | Leung, YYJ: leungjy@hku.hk | - |
dc.identifier.email | Hui, LL: huic@hkucc.hku.hk | - |
dc.identifier.email | Leung, GM: gmleung@hku.hk | - |
dc.identifier.email | Schooling, CM: cms1@hkucc.hku.hk | - |
dc.identifier.authority | Au Yeung, SL=rp02224 | - |
dc.identifier.authority | Kwok, MK=rp02051 | - |
dc.identifier.authority | Leung, YYJ=rp01817 | - |
dc.identifier.authority | Hui, LL=rp01698 | - |
dc.identifier.authority | Leung, GM=rp00460 | - |
dc.identifier.authority | Schooling, CM=rp00504 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1371/journal.pone.0228737 | - |
dc.identifier.pmid | 32045441 | - |
dc.identifier.pmcid | PMC7012438 | - |
dc.identifier.scopus | eid_2-s2.0-85079316984 | - |
dc.identifier.hkuros | 309302 | - |
dc.identifier.volume | 15 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | article no. e0228737 | - |
dc.identifier.epage | article no. e0228737 | - |
dc.identifier.isi | WOS:000534633200035 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 1932-6203 | - |