Dietary intake, a major contributor to the global obesity epidemic, is a complex phenotype partially affected by innate physiological processes. However, previous genome-wide association studies have only implicated a few loci in variability of dietary intake. 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 identifying 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 based on clinical and physiological similarities yields three main genetic clusters with distinct associations with obesity and type 2 diabetes. Overall, these results enhance biological understanding of dietary composition, highlight neural mechanisms, and support functional follow-up experiments.
Keywords: diet, genome-wide association study, Nutrition, GWAS, Genetics, Dietary Intake
Merino, Jordi and Dashti, Hassan S. and Sarnowski, Chloé and Lane, Jacqueline M. and Udler, Miriam S. and Todorov, Petar V. and Song, Yanwei and Wang, Heming and Kim, Jaegil and Tucker, Chandler and Campbell, John and Tanaka, Toshiko and Chu, Audrey Y. and Tsai, Linus and Pers, Tune H. and Chasman, Daniel I. and Dupuis, Josée and Rutter, Martin K. and Florez, Jose C. and Saxena, Richa, Genetic Analysis of Dietary Intake Identifies New Loci and Functional Links with Metabolic Traits (June 26, 2019). Available at SSRN: https://ssrn.com/abstract=3409949 or http://dx.doi.org/10.2139/ssrn.3409949
This version of the paper has not been formally peer reviewed.
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