Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake
Creators: name: Chasman, Daniel I.
name: Kritchevsky, Stephen B.
name: Raitakari, Olli
name: Luan, Jia N.An
name: Forouhi, Nita G.
name: De Oliveira Otto, Marcia C.
name: Schrack, Jennifer A.
name: McKeown, Nicola M.
name: Van Rooij, Frank J.A.
name: Rotter, Jerome I.
name: Witteman, Jacqueline C.M.
name: Siscovick, David S.
name: Uitterlinden, André G.
name: Wojczynski, Mary K.
name: Langenberg, Claudia
name: Wareham, Nicholas J.
name: Emilsson, Valur
name: Orho-Melander, Marju
name: Zhao, Jing Hua
name: Semba, Richard D.
name: Renstrom, Frida
name: Qi, Lu
name: Frazier-Wood, Alexis C.
name: Viikari, Jorma
name: Lohman, Kurt K.
name: Tanaka, Toshiko
name: Barroso, Inês
name: Khaw, Kay Tee
name: Bandinelli, Stefania
name: Ordovas, Jose M.
name: Singleton, Andrew
name: Deloukas, Panos
name: Chu, Audrey Y.
name: Loos, Terho Lehtimäki Ruth J.F.
name: Stirrups, Kathleen
name: Franks, Paul W.
name: Houston, Denise K.
name: Kähönen, Mika
name: Mikkilä, Vera
name: Kalafati, Ioanna Panagiota
name: Ferrucci, Luigi
name: Ye, Zheng
name: Arnett, Donna K.
name: Hallmans, Goran
name: Feitosa, Mary F.
name: Zillikens, M. Carola
name: North, Kari E.
name: Manichaikul, Ani
name: Borecki, Ingrid B.
name: Liu, Yongmei
name: Lemaitre, Rozenn N.
name: Franco, Oscar H.
name: Mozaffarian, Dariush
name: Cupples, L. Adrienne
name: Lyytikäinen, Leo Pekka
name: Kanoni, Stavroula
name: Hu, Frank B.
name: Nettleton, Jennifer A.
name: Hofman, Albert
name: Johnson, Andrew
name: Johansson, Ingegerd
name: Dimitriou, Maria
name: Sonestedt, Emily
name: Ngwa, Julius S.
name: Dedoussis, George
name: Dhurandhar, Emily J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: 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).