Genetic analysis of dietary intake identifies new loci and functional links with metabolic traits

Jordi Merino, Hassan S. Dashti, Chloé Sarnowski, Jacqueline M. Lane, Petar V. Todorov, Miriam S. Udler, Yanwei Song, Heming Wang, Jaegil Kim, Chandler Tucker, John Campbell, Toshiko Tanaka, Audrey Y. Chu, Linus Tsai, Tune H. Pers, Daniel I. Chasman, Martin K. Rutter, Josée Dupuis (), Jose C. Florez () and Richa Saxena ()
Additional contact information
Jordi Merino: Massachusetts General Hospital
Hassan S. Dashti: Massachusetts General Hospital
Chloé Sarnowski: Boston University School of Public Health
Jacqueline M. Lane: Massachusetts General Hospital
Petar V. Todorov: University of Copenhagen
Miriam S. Udler: Massachusetts General Hospital
Yanwei Song: Massachusetts General Hospital
Heming Wang: Broad Institute of MIT and Harvard
Jaegil Kim: Massachusetts General Hospital
Chandler Tucker: Massachusetts General Hospital
John Campbell: Beth Israel Deaconess Medical Center, Harvard Medical School
Toshiko Tanaka: National Institute on Aging
Audrey Y. Chu: Merck
Linus Tsai: Beth Israel Deaconess Medical Center, Harvard Medical School
Tune H. Pers: Boston University School of Public Health
Daniel I. Chasman: Brigham and Women’s Hospital and Harvard Medical School
Martin K. Rutter: University of Manchester
Josée Dupuis: Boston University School of Public Health
Jose C. Florez: Massachusetts General Hospital
Richa Saxena: Massachusetts General Hospital

Nature Human Behaviour, 2022, vol. 6, issue 1, 155-163

Abstract: Abstract Dietary intake is a major contributor to the global obesity epidemic and represents a complex behavioural phenotype that is partially affected by innate biological differences. Here, we present a multivariate genome-wide association analysis of overall variation in dietary intake to account for the correlation between dietary carbohydrate, fat and protein in 282,271 participants of European ancestry from the UK Biobank (n = 191,157) and Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 91,114), and identify 26 distinct genome-wide significant loci. Dietary intake signals map exclusively to specific brain regions and are enriched for genes expressed in specialized subtypes of GABAergic, dopaminergic and glutamatergic neurons. We identified two main clusters of genetic variants for overall variation in dietary intake that were differently associated with obesity and coronary artery disease. These results enhance the biological understanding of interindividual differences in dietary intake by highlighting neural mechanisms, supporting functional follow-up experiments and possibly providing new avenues for the prevention and treatment of prevalent complex metabolic diseases.

Date: 2022
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DOI: 10.1038/s41562-021-01182-w

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