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Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis

Borges, MC; Barros, AJD; Ferreira, DLS; Casas, JP; Horta, BL; Kivimaki, M; Kumari, M; ... Hingorani, AD; + view all (2017) Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis. Circulation: Cardiovascular Genetics , 10 , Article e001837. 10.1161/CIRCGENETICS.117.001837. Green open access

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Abstract

BACKGROUND: Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. METHODS AND RESULTS: We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis-acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population. CONCLUSIONS: Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant.

Type: Article
Title: Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCGENETICS.117.001837
Publisher version: https://doi.org/10.1161/CIRCGENETICS.117.001837
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Mendelian Randomization Analysis, adiponectin, cardiovascular disease, insulin, metabolism, metabolomics
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Health Informatics
URI: http://discovery.ucl.ac.uk/id/eprint/10040274
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