Multi-trait genome-wide association meta-analysis of dietary intake identifies new loci and genetic and functional links with metabolic traits
Year: 2019
Type: preprint
Study design: Observational Study
Abstract: ABSTRACT Dietary intake, a major contributor to the global obesity epidemic 1–5 , is a complex phenotype partially affected by innate physiological processes. 6–11 However, previous genome-wide association studies (GWAS) have only implicated a few loci in variability of dietary composition. 12–14 Here, we present a multi-trait genome-wide association meta-analysis of inter-individual variation in dietary intake in 283,119 European-ancestry participants from UK Biobank and CHARGE consortium, and identify 96 genome-wide significant loci. Dietary intake signals map to different brain tissues and are enriched for genes expressed in β1-tanycytes and serotonergic and GABAergic neurons. We also find enrichment of biological pathways related to neurogenesis. Integration of cell-line and brain-specific epigenomic annotations identify 15 additional loci. Clustering of genome-wide significant variants yields three main genetic clusters with distinct associations with obesity and type 2 diabetes (T2D). Overall, these results enhance biological understanding of dietary composition, highlight neural mechanisms, and support functional follow-up experiments.
DOI: 10.1101/623728
Authors: Jordi Merino, Hassan S. Dashti, Chloé Sarnowski, Jacqueline M. Lane, Miriam S. Udler, Petar V. Todorov, Yanwei Song, Heming Wang, Jaegil Kim, Chandler Tucker, John Campbell, Toshiko Tanaka, Audrey Y. Chu, Linus Tsai, Tune H. Pers, Daniel I. Chasman, Josée Dupuis, Martin K. Rutter, Jose C. Florez, Richa Saxena
Institutions: Broad Institute, Harvard University, Massachusetts General Hospital, Boston University, University of Copenhagen, Novo Nordisk Foundation, Novo Nordisk Foundation Center for Basic Metabolic Research, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, University of Virginia, National Institute on Aging, Merck & Co., Inc., Rahway, NJ, USA (United States), Statens Serum Institut, Manchester Academic Health Science Centre, University of Manchester, Manchester University NHS Foundation Trust
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: American Diabetes Association, European Commission, Lundbeckfonden, Novo Nordisk, Novo Nordisk Fonden, H. Lundbeck A/S, National Institutes of Health, Horizon 2020 Framework Programme, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1017378214, G2585873956, G2651529389, Impact of Malatonin, Food Timing and Receptor Variant on Type 2 Diabetes Risk, G3345895242, Molecular and functional taxonomy of vagal motor neurons, G4937468798, Melatonin and Receptor Gene Variant: Linking Circadian System and Type 2 Diabetes, G5520316217, G5573126869, Rare Sequence Variation and Diabetes Quantitative Traits, G6329715174, Interplay between genetic determinants of glycaemia, type 2 diabetes and cardiovascular disease in interaction with dietary and lifestyle factors, G6766900198, G8133917136, G8512683158, G8858395165, G9000079831, Training in Sleep, Circadian, and Respiratory Neurobiology, Genetics of chronotype and impact on metabolic disease, G959094345
OpenAlex ID: W2946858967