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; Richa Saxena

doi:10.1038/s41562-021-01182-w

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

Nat Hum Behav. 2022 Jan;6(1):155-163. doi: 10.1038/s41562-021-01182-w. Epub 2021 Aug 23.

Authors

Jordi Merino^#^{1

2

3

4

5}, Hassan S Dashti^#^{1

2

6}, Chloé Sarnowski^#⁷, Jacqueline M Lane^{1

2

6}, Petar V Todorov⁸, Miriam S Udler^{1

2

3

4}, Yanwei Song^{1

2}, Heming Wang^{2

9

10}, Jaegil Kim³, Chandler Tucker¹, John Campbell^{11

12}, Toshiko Tanaka¹³, Audrey Y Chu¹⁴, Linus Tsai¹¹, Tune H Pers^{7

15}, Daniel I Chasman^{16

17}, Martin K Rutter^{18

19}, Josée Dupuis²⁰, Jose C Florez^{21

22

23

24}, Richa Saxena^{25

26

27

28}

Affiliations

¹ Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
² Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³ Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
⁴ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁵ Research Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, Institut d'Investigació Sanitària Pere Virgili, Reus, Spain.
⁶ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁸ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁹ Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁰ Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
¹¹ Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹² Department of Biology, University of Virginia, Charlottesville, VA, USA.
¹³ Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
¹⁴ Merck, Boston, MA, USA.
¹⁵ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
¹⁶ Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁷ Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁸ Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
¹⁹ Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
²⁰ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. dupuis@bu.edu.
²¹ Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. jcflorez@partners.org.
²² Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. jcflorez@partners.org.
²³ Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. jcflorez@partners.org.
²⁴ Department of Medicine, Harvard Medical School, Boston, MA, USA. jcflorez@partners.org.
²⁵ Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. rsaxena@mgh.harvard.edu.
²⁶ Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. rsaxena@mgh.harvard.edu.
²⁷ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. rsaxena@mgh.harvard.edu.
²⁸ Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA. rsaxena@mgh.harvard.edu.

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Diet*
Genetic Loci*
Genome-Wide Association Study
Genotype
Humans
Nuclear Proteins / genetics
Obesity / genetics*
Phenotype
Polymorphism, Single Nucleotide

Substances

NSL1 protein, human
Nuclear Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding