Multi-trait genome-wide association meta-analysis of dietary intake identifies new loci and genetic and functional links with metabolic traits

Merino, J.; Dashti, H. S.; Sarnowski, C.; Lane, J. M.; Udler, M. S.; Todorov, P. V.; Song, Y.; Wang, H.; Kim, J.; Tucker, C.; Campbell, J.; Tanaka, T.; Chu, A. Y.; Tsai, L.; Pers, T. H.; Chasman, D. I.; Dupuis, J.; Rutter, M. K.; Florez, J. C.; Saxena, R.

doi:10.1101/623728

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bioRxiv · 10.1101/623728

Multi-trait genome-wide association meta-analysis of dietary intake identifies new loci and genetic and functional links with metabolic traits

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Abstract

Dietary intake, a major contributor to the global obesity epidemic1-5, 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 {beta}1-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.

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Merino, J., Dashti, H. S., Sarnowski, C., Lane, J. M., Udler, M. S., Todorov, P. V., Song, Y., Wang, H., Kim, J., Tucker, C., Campbell, J., Tanaka, T., Chu, A. Y., Tsai, L., Pers, T. H., Chasman, D. I., Dupuis, J., Rutter, M. K., Florez, J. C., Saxena, R.. 2019-05-01. Multi-trait genome-wide association meta-analysis of dietary intake identifies new loci and genetic and functional links with metabolic traits. https://doi.org/10.1101/623728

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