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

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

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2013-06

10/f23bpd

PMID: 23636237 PMCID: PMC3652928

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

Automatic Tags

Humans; Obesity; Body Mass Index; Energy Intake; Genotype; Atherosclerosis; Dietary Carbohydrates; Prospective Studies; Life Style; Surveys and Questionnaires; Genetic Predisposition to Disease; Dietary Proteins; European Continental Ancestry Group; Gene-Environment Interaction; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Fibroblast Growth Factors; Alleles; Quantitative Trait Loci

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