Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake.

Abstract

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 × 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 (β ± SE: 0.25 ± 0.04%; P = 1.68 × 10(-8)) and lower fat (β ± SE: -0.21 ± 0.04%; P = 1.57 × 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 (β ± SE: 0.10 ± 0.02%; P = 9.96 × 10(-10)), independent of BMI (after adjustment for BMI, β ± SE: 0.08 ± 0.02%; P = 3.15 × 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).

• Authors: Toshiko Tanaka, Julius S Ngwa, Frank J A van Rooij, M Carola Zillikens, Mary K Wojczynski, Alexis C Frazier-Wood, Denise K Houston, Stavroula Kanoni, Rozenn N Lemaitre, Jian'an Luan, Vera Mikkilä, Frida Renstrom, Emily Sonestedt, Jing Hua Zhao, Audrey Y Chu, Lu Qi, Daniel I Chasman, Marcia C de Oliveira Otto, Emily J Dhurandhar, Mary F Feitosa, Ingegerd Johansson, Kay-Tee Khaw, Kurt K Lohman, Ani Manichaikul, Nicola M McKeown, Dariush Mozaffarian, Andrew Singleton, Kathleen Stirrups, Jorma Viikari, Zheng Ye, Stefania Bandinelli, Inês Barroso, Panos Deloukas, Nita G Forouhi, Albert Hofman, Yongmei Liu, Leo-Pekka Lyytikäinen, Kari E North, Maria Dimitriou, Goran Hallmans, Mika Kähönen, Claudia Langenberg, Jose M Ordovas, André G Uitterlinden, Frank B Hu, Ioanna-Panagiota Kalafati, Olli Raitakari, Oscar H Franco, Andrew Johnson, Valur Emilsson, Jennifer A Schrack, Richard D Semba, David S Siscovick, Donna K Arnett, Ingrid B Borecki, Paul W Franks, Stephen B Kritchevsky, Terho Lehtimäki, Ruth J F Loos, Marju Orho-Melander, Jerome I Rotter, Nicholas J Wareham, Jacqueline C M Witteman, Luigi Ferrucci, George Dedoussis, L Adrienne Cupples, Jennifer A Nettleton
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 97 Issue 6 Pg. 1395-402 (Jun 2013) ISSN: 1938-3207 [Electronic] United States
• PMID: 23636237 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Dietary Carbohydrates
• Dietary Fats
• Dietary Proteins
• fibroblast growth factor 21
• Fibroblast Growth Factors

Topics

• Alleles
• Atherosclerosis (genetics)
• Body Mass Index
• Dietary Carbohydrates (administration & dosage)
• Dietary Fats (administration & dosage)
• Dietary Proteins (administration & dosage)
• Energy Intake
• Fibroblast Growth Factors (blood, genetics)
• Follow-Up Studies
• Gene-Environment Interaction
• Genetic Predisposition to Disease
• Genome-Wide Association Study (methods)
• Genotype
• Humans
• Life Style
• Obesity (genetics)
• Polymorphism, Single Nucleotide
• Prospective Studies
• Quantitative Trait Loci
• Surveys and Questionnaires
• White People (genetics)