TY - JOUR
T1 - Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake
AU - Tanaka, Toshiko
AU - Ngwa, Julius S.
AU - Van Rooij, Frank J.A.
AU - Zillikens, M. Carola
AU - Wojczynski, Mary K.
AU - Frazier-Wood, Alexis C.
AU - Houston, Denise K.
AU - Kanoni, Stavroula
AU - Lemaitre, Rozenn N.
AU - Luan, Jia N.An
AU - Mikkilä, Vera
AU - Renstrom, Frida
AU - Sonestedt, Emily
AU - Zhao, Jing Hua
AU - Chu, Audrey Y.
AU - Qi, Lu
AU - Chasman, Daniel I.
AU - De Oliveira Otto, Marcia C.
AU - Dhurandhar, Emily J.
AU - Feitosa, Mary F.
AU - Johansson, Ingegerd
AU - Khaw, Kay Tee
AU - Lohman, Kurt K.
AU - Manichaikul, Ani
AU - McKeown, Nicola M.
AU - Mozaffarian, Dariush
AU - Singleton, Andrew
AU - Stirrups, Kathleen
AU - Viikari, Jorma
AU - Ye, Zheng
AU - Bandinelli, Stefania
AU - Barroso, Inês
AU - Deloukas, Panos
AU - Forouhi, Nita G.
AU - Hofman, Albert
AU - Liu, Yongmei
AU - Lyytikäinen, Leo Pekka
AU - North, Kari E.
AU - Dimitriou, Maria
AU - Hallmans, Goran
AU - Kähönen, Mika
AU - Langenberg, Claudia
AU - Ordovas, Jose M.
AU - Uitterlinden, André G.
AU - Hu, Frank B.
AU - Kalafati, Ioanna Panagiota
AU - Raitakari, Olli
AU - Franco, Oscar H.
AU - Johnson, Andrew
AU - Emilsson, Valur
AU - Schrack, Jennifer A.
AU - Semba, Richard D.
AU - Siscovick, David S.
AU - Arnett, Donna K.
AU - Borecki, Ingrid B.
AU - Franks, Paul W.
AU - Kritchevsky, Stephen B.
AU - Loos, Terho Lehtimäki Ruth J.F.
AU - Orho-Melander, Marju
AU - Rotter, Jerome I.
AU - Wareham, Nicholas J.
AU - Witteman, Jacqueline C.M.
AU - Ferrucci, Luigi
AU - Dedoussis, George
AU - Cupples, L. Adrienne
AU - Nettleton, Jennifer A.
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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).
AB - 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).
UR - https://www.scopus.com/pages/publications/84875922294
UR - https://www.scopus.com/pages/publications/84875922294#tab=citedBy
U2 - 10.3945/ajcn.112.052183
DO - 10.3945/ajcn.112.052183
M3 - Article
C2 - 23636237
AN - SCOPUS:84875922294
SN - 0002-9165
VL - 97
SP - 1395
EP - 1402
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 6
ER -
Good health and well being
Affordable and clean energy