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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. and Luan, Jian'an, et al. (2013) In American Journal of Clinical Nutrition 97(6). p.1395-1402
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 x 10(-6) were identified and taken forward to... (More)
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 x 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 (beta +/- SE: 0.25 +/- 0.04%; P = 1.68 x 10(-8)) and lower fat (beta = SE: -0.21 +/- 0.04%; P = 1.57 x 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 (beta +/- SE: 0.10 +/- 0.02%; P = 9.96 x 10(-10)), independent of BMI (after adjustment for BMI, beta +/- SE: 0.08 +/- 0.02%; P = 3.15 x 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). (Less)
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American Journal of Clinical Nutrition
volume
97
issue
6
pages
1395 - 1402
publisher
American Society for Clinical Nutrition
external identifiers
  • wos:000319371500030
  • scopus:84875922294
ISSN
1938-3207
DOI
10.3945/ajcn.112.052183
language
English
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yes
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a54b9548-f630-4c17-b90a-b950781ab7c0 (old id 3930596)
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2013-08-01 07:37:03
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2019-02-10 03:53:19
@article{a54b9548-f630-4c17-b90a-b950781ab7c0,
  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 &lt; 5 x 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 (beta +/- SE: 0.25 +/- 0.04%; P = 1.68 x 10(-8)) and lower fat (beta = SE: -0.21 +/- 0.04%; P = 1.57 x 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 &lt; 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 (beta +/- SE: 0.10 +/- 0.02%; P = 9.96 x 10(-10)), independent of BMI (after adjustment for BMI, beta +/- SE: 0.08 +/- 0.02%; P = 3.15 x 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).},
  author       = {Tanaka, Toshiko and Ngwa, Julius S. and van Rooij, Frank J. A. and Zillikens, M. Carola and Wojczynski, Mary K. and Frazier-Wood, Alexis C. and Houston, Denise K. and Kanoni, Stavroula and Lemaitre, Rozenn N. and Luan, Jian'an and Mikkila, Vera and Renström, Frida and Sonestedt, Emily and Zhao, Jing Hua and Chu, Audrey Y. and Qi, Lu and Chasman, Daniel I. and Otto, Marcia C. de Oliveira and Dhurandhar, Emily J. and Feitosa, Mary F. and Johansson, Ingegerd and Khaw, Kay-Tee and Lohman, Kurt K. and Manichaikul, Ani and McKeown, Nicola M. and Mozaffarian, Dariush and Singleton, Andrew and Stirrups, Kathleen and Viikari, Jorma and Ye, Zheng and Bandinelli, Stefania and Barroso, Ines and Deloukas, Panos and Forouhi, Nita G. and Hofman, Albert and Liu, Yongmei and Lyytikainen, Leo-Pekka and North, Kari E. and Dimitriou, Maria and Hallmans, Goran and Kahonen, Mika and Langenberg, Claudia and Ordovas, Jose M. and Uitterlinden, Andre G. and Hu, Frank B. and Kalafati, Ioanna-Panagiota and Raitakari, Olli and Franco, Oscar H. and Johnson, Andrew and Emilsson, Valur and Schrack, Jennifer A. and Semba, Richard D. and Siscovick, David S. and Arnett, Donna K. and Borecki, Ingrid B. and Franks, Paul and Kritchevsky, Stephen B. and Lehtimaki, Terho and Loos, Ruth J. F. and Orho-Melander, Marju and Rotter, Jerome I. and Wareham, Nicholas J. and Witteman, Jacqueline C. M. and Ferrucci, Luigi and Dedoussis, George and Cupples, L. Adrienne and Nettleton, Jennifer A.},
  issn         = {1938-3207},
  language     = {eng},
  number       = {6},
  pages        = {1395--1402},
  publisher    = {American Society for Clinical Nutrition},
  series       = {American Journal of Clinical Nutrition},
  title        = {Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake},
  url          = {http://dx.doi.org/10.3945/ajcn.112.052183},
  volume       = {97},
  year         = {2013},
}