Publikation
Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake
Wissenschaftlicher Artikel/Review - 01.05.2013
Nettleton Jennifer A, Johnson Andrew, Franco Oscar H, Raitakari Olli, Kalafati Ioanna-Panagiota, Hu Frank B, Uitterlinden André G, Ordovas Jose M, Langenberg Claudia, Kähönen Mika, Hallmans Göran, Dimitriou Maria, North Kari E, Lyytikäinen Leo-Pekka, Liu Yongmei, Emilsson Valur, Schrack Jennifer A, Semba Richard D, Cupples L Adrienne, Dedoussis George, Ferrucci Luigi, Witteman Jacqueline C M, Wareham Nicholas J, Rotter Jerome I, Orho-Melander Marju, Loos Ruth J F, Lehtimäki Terho, Kritchevsky Stephen B, Franks Paul W, Borecki Ingrid B, Arnett Donna K, Siscovick David S, Hofman Albert, Forouhi Nita G, Deloukas Panos, Chu Audrey Y, Zhao Jing Hua, Sonestedt Emily, Renström Frida, Mikkilä Vera, Luan Jian'an, Lemaitre Rozenn N, Kanoni Stavroula, Houston Denise K, Frazier-Wood Alexis C, Wojczynski Mary K, Zillikens M Carola, van Rooij Frank J A, Ngwa Julius S, Qi Lu, Chasman Daniel I, de Oliveira Otto Marcia C, Barroso Inês, Bandinelli Stefania, Ye Zheng, Viikari Jorma, Stirrups Kathleen, Singleton Andrew, Mozaffarian Dariush, McKeown Nicola M, Manichaikul Ani, Lohman Kurt K, Khaw Kay-Tee, Johansson Ingegerd, Feitosa Mary F, Dhurandhar Emily J, Tanaka Toshiko
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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 × 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).