Large-scale metabolomic profiling and incident non-alcoholic fatty liver disease
Eloi Gagnon,
Hasanga D. Manikpurage,
Patricia L. Mitchell,
Arnaud Girard,
Émilie Gobeil,
Jérôme Bourgault,
Frédéric Bégin,
André Marette,
Sébastien Thériault,
Benoit J. Arsenault
Affiliations
Eloi Gagnon
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada
Hasanga D. Manikpurage
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada
Patricia L. Mitchell
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada
Arnaud Girard
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada
Émilie Gobeil
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada
Jérôme Bourgault
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada
Frédéric Bégin
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada
André Marette
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada; Department of Medicine, Faculty of Medicine, Université Laval, Québec (QC), Canada
Sébastien Thériault
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec (QC), Canada
Benoit J. Arsenault
Centre de Recherche de L’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec (QC), Canada; Department of Medicine, Faculty of Medicine, Université Laval, Québec (QC), Canada; Corresponding author
Summary: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease with no specific drug therapy. High-throughput metabolomics present an unprecedented opportunity to identify biomarkers and potentially causal risk factors for NAFLD. Here, we determined the impact of 21 circulating metabolites, 17 lipids, and 132 lipoprotein particle characteristics on NAFLD combining prospective observational and two-sample Mendelian randomization (MR) analyses in 121,032 UK Biobank participants. We identified several metabolic factors associated with NAFLD risk in observational and MR analyses including triglyceride-rich and high-density lipoprotein particles composition, as well as the ratio of polyunsaturated fatty acids to total fatty acids. This study, is one of the largest to investigate incident NAFLD, provides concordant observational and genetic evidence that therapies aimed at reducing circulating triglycerides and increasing large HDL particles, as well as interventions aimed at increasing polyunsaturated fatty acid content may warrant further investigation into NAFLD prevention and treatment.
