Journal
AMERICAN JOURNAL OF CLINICAL NUTRITION
Volume 97, Issue 6, Pages 1395-1402Publisher
OXFORD UNIV PRESS
DOI: 10.3945/ajcn.112.052183
Keywords
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Funding
- National Institutes of Health
- NIH Roadmap for Medical Research
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging
- National Center of Advancing Translational Technologies
- US Department of Agriculture
- Medical Research Council UK
- Wellcome Trust
- Italian Ministry of Health
- Netherlands Organisation of Scientific Research NWO Investments
- Research Institute for Diseases in the Elderly (RIDE2) [014-93-015]
- Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA), Rotterdam
- Netherlands Organization for the Health Research and Development
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture, and Science
- Ministry for Health, Welfare, and Sports
- European Commission
- Municipality of Rotterdam
- Academy of Finland
- Social Insurance Institution of Finland
- Swedish Heart-Lung Foundation
- Swedish Diabetes Association
- Swedish Research Council
- City of Malmo
- Pahlsson Foundation
- Affymetrix Inc
- Robert Dawson Evans Endowment
- Doris Duke Charitable Foundation
- Centre de Recherche Medicale de l'Universite de Sherbrooke (CRMUS)
- Canadian Institute of Health Research (CHIR)
- Erasmus Medical Center
- Erasmus University
- Kuopio University Hospital
- Tampere University Hospital
- Turku University Hospital
- Juho Vainio Foundation
- Paavo Nurmi Foundation
- Finnish Foundation of Cardiovascular Research
- Finnish Cultural Foundation
- Tampere Tuberculosis Foundation
- Emil Aaltonen Foundation
- Novo Nordisk
- Umea University
- Heart Foundation of Northern Sweden, Region Shine
- Cancer Research UK
- Cancer Research UK [14136] Funding Source: researchfish
- Medical Research Council [G1000143, MC_UU_12015/1, MC_UP_A100_1003, MC_U106188470, MC_U106179471, MC_UU_12015/5, G0401527] Funding Source: researchfish
- MRC [MC_UU_12015/1, MC_UU_12015/5, MC_U106188470, MC_UP_A100_1003] Funding Source: UKRI
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Background: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. Design: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 x 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n 7724) provided additional replication data. Results: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (beta +/- SE: 0.25 +/- 0.04%; P = 1.68 x 10(-8)) and lower fat (beta = SE: -0.21 +/- 0.04%; P = 1.57 x 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI) increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (beta +/- SE: 0.10 +/- 0.02%; P = 9.96 x 10(-10)), independent of BMI (after adjustment for BMI, beta +/- SE: 0.08 +/- 0.02%; P = 3.15 x 10(-7)). Conclusion: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).
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