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Genetic Analysis of Dietary Intake Identifies New Loci and Functional Links with Metabolic Traits

55 Pages Posted: 26 Jun 2019 Publication Status: Review Complete

See all articles by Jordi Merino

Jordi Merino

Massachusetts General Hospital - Center for Genomic Medicine

Hassan S. Dashti

Massachusetts General Hospital - Center for Genomic Medicine

Chloé Sarnowski

Boston University - Department of Biostatistics

Jacqueline M. Lane

Massachusetts General Hospital - Center for Genomic Medicine

Miriam S. Udler

Massachusetts General Hospital - Center for Genomic Medicine

Petar V. Todorov

University of Copenhagen - The Novo Nordisk Foundation Center for Basic Metabolic Research

Yanwei Song

Massachusetts General Hospital - Center for Genomic Medicine

Heming Wang

Massachusetts Institute of Technology and Harvard University - Programs in Metabolism and Medical & Population Genetics

Jaegil Kim

Massachusetts General Hospital

Chandler Tucker

Massachusetts General Hospital - Center for Genomic Medicine

John Campbell

University of Virginia

Toshiko Tanaka

National Institute on Aging (NIA)

Audrey Y. Chu

Merck & Co., Inc.

Linus Tsai

Harvard Medical School - Division of Endocrinology, Diabetes, and Metabolism

Tune H. Pers

University of Copenhagen - The Novo Nordisk Foundation Center for Basic Metabolic Research

Daniel I. Chasman

Brigham and Women's Hospital

Josée Dupuis

Boston University - Department of Biostatistics

Martin K. Rutter

The University of Manchester - Manchester Academic Health Science Centre

Jose C. Florez

Massachusetts General Hospital - Center for Genomic Medicine

Richa Saxena

Massachusetts General Hospital - Center for Genomic Medicine

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Abstract

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

Suggested Citation

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.

Jordi Merino (Contact Author)

Massachusetts General Hospital - Center for Genomic Medicine ( email )

185 Cambridge Street
Boston, MA 02114
United States

Hassan S. Dashti

Massachusetts General Hospital - Center for Genomic Medicine

55 Fruit Street Boston
Boston, MA 02114
United States

Chloé Sarnowski

Boston University - Department of Biostatistics

Boston, MA
United States

Jacqueline M. Lane

Massachusetts General Hospital - Center for Genomic Medicine

185 Cambridge Street
Boston, MA 02114
United States

Miriam S. Udler

Massachusetts General Hospital - Center for Genomic Medicine

185 Cambridge Street
Boston, MA 02114
United States

Petar V. Todorov

University of Copenhagen - The Novo Nordisk Foundation Center for Basic Metabolic Research

Blegdamsvej 3B
Copenhagen, DK-2200
Denmark

Yanwei Song

Massachusetts General Hospital - Center for Genomic Medicine

185 Cambridge Street
Boston, MA 02114
United States

Heming Wang

Massachusetts Institute of Technology and Harvard University - Programs in Metabolism and Medical & Population Genetics

Cambridge, MA
United States

Jaegil Kim

Massachusetts General Hospital

55 Fruit Street Boston
Boston, MA 02114
United States

Chandler Tucker

Massachusetts General Hospital - Center for Genomic Medicine

185 Cambridge Street
Boston, MA 02114
United States

John Campbell

University of Virginia

1400 University Ave
Charlottesville, VA 22903
United States

Toshiko Tanaka

National Institute on Aging (NIA)

Building 31, Room 5C27
31 Center Drive, MSC 2292
Bethesda, MD 20892
United States

Audrey Y. Chu

Merck & Co., Inc.

United States

Linus Tsai

Harvard Medical School - Division of Endocrinology, Diabetes, and Metabolism

United States

Tune H. Pers

University of Copenhagen - The Novo Nordisk Foundation Center for Basic Metabolic Research

Blegdamsvej 3B
Copenhagen, DK-2200
Denmark

Daniel I. Chasman

Brigham and Women's Hospital

75 Francis St.
Boston, MA 02115
United States

Josée Dupuis

Boston University - Department of Biostatistics

Boston, MA
United States

Martin K. Rutter

The University of Manchester - Manchester Academic Health Science Centre

United Kingdom

Jose C. Florez

Massachusetts General Hospital - Center for Genomic Medicine

185 Cambridge Street
Boston, MA 02114
United States

Richa Saxena

Massachusetts General Hospital - Center for Genomic Medicine

185 Cambridge Street
Boston, MA 02114
United States

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