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Genomic analysis of diet composition finds novel loci and associations with health and lifestyle.

Accepted version
Peer-reviewed

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Authors

Meddens, S Fleur W 
de Vlaming, Ronald 
Bowers, Peter 
Burik, Casper AP 
Linnér, Richard Karlsson  ORCID logo  https://orcid.org/0000-0001-7839-2858

Abstract

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10-8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10-5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1-0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction.

Description

Keywords

Body Mass Index, Diabetes Mellitus, Type 2, Diet, Genome-Wide Association Study, Genomics, Humans, Life Style

Journal Title

Mol Psychiatry

Conference Name

Journal ISSN

1359-4184
1476-5578

Volume Title

26

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Medical Research Council (MC_UU_12015/5)
Medical Research Council (MC_UU_12015/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
European Commission (37197)
MRC (MC_UU_00006/3)
In section 13.1 of the supplementary information: Nick J Wareham and Nita G Forouhi acknowledge support from the National Institute for Health Research Cambridge Biomedical Research Centre [IS-BRC-1215-20014] and NJW is an NIHR Senior Investigator.
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