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

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Tanaka, Toshiko (author)

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

Article/chapterEnglish2013

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Elsevier BV,2013

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LIBRIS-ID:oai:lup.lub.lu.se:a54b9548-f630-4c17-b90a-b950781ab7c0
https://lup.lub.lu.se/record/3930596URI
https://doi.org/10.3945/ajcn.112.052183DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-76247URI

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Language:English
Summary in:English

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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 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).

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Ngwa, Julius S. (author)
van Rooij, Frank J. A. (author)
Zillikens, M. Carola (author)
Wojczynski, Mary K. (author)
Frazier-Wood, Alexis C. (author)
Houston, Denise K. (author)
Kanoni, Stavroula (author)
Lemaitre, Rozenn N. (author)
Luan, Jian'an (author)
Mikkila, Vera (author)
Renström, FridaLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-frm (author)
Sonestedt, EmilyLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)medf-eso (author)
Zhao, Jing Hua (author)
Chu, Audrey Y. (author)
Qi, Lu (author)
Chasman, Daniel I. (author)
Otto, Marcia C. de Oliveira (author)
Dhurandhar, Emily J. (author)
Feitosa, Mary F. (author)
Johansson, IngegerdUmeå universitet,Institutionen för odontologi(Swepub:umu)injo0003 (author)
Khaw, Kay-Tee (author)
Lohman, Kurt K. (author)
Manichaikul, Ani (author)
McKeown, Nicola M. (author)
Mozaffarian, Dariush (author)
Singleton, Andrew (author)
Stirrups, Kathleen (author)
Viikari, Jorma (author)
Ye, Zheng (author)
Bandinelli, Stefania (author)
Barroso, Ines (author)
Deloukas, Panos (author)
Forouhi, Nita G. (author)
Hofman, Albert (author)
Liu, Yongmei (author)
Lyytikainen, Leo-Pekka (author)
North, Kari E. (author)
Dimitriou, Maria (author)
Hallmans, GöranUmeå universitet,Näringsforskning,Enheten för biobanksforskning(Swepub:umu)goha0001 (author)
Kahonen, Mika (author)
Langenberg, Claudia (author)
Ordovas, Jose M. (author)
Uitterlinden, Andre G. (author)
Hu, Frank B. (author)
Kalafati, Ioanna-Panagiota (author)
Raitakari, Olli (author)
Franco, Oscar H. (author)
Johnson, Andrew (author)
Emilsson, Valur (author)
Schrack, Jennifer A. (author)
Semba, Richard D. (author)
Siscovick, David S. (author)
Arnett, Donna K. (author)
Borecki, Ingrid B. (author)
Franks, PaulUmeå universitet,Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Medicin(Swepub:umu)pafr0003 (author)
Kritchevsky, Stephen B. (author)
Lehtimaki, Terho (author)
Loos, Ruth J. F. (author)
Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor (author)
Rotter, Jerome I. (author)
Wareham, Nicholas J. (author)
Witteman, Jacqueline C. M. (author)
Ferrucci, Luigi (author)
Dedoussis, George (author)
Cupples, L. Adrienne (author)
Nettleton, Jennifer A. (author)
Genetisk och molekylär epidemiologiForskargrupper vid Lunds universitet (creator_code:org_t)

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In:American Journal of Clinical Nutrition: Elsevier BV97:6, s. 1395-14021938-32070002-9165

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By the author/editor: Tanaka, Toshiko; Ngwa, Julius S.; van Rooij, Frank ...; Zillikens, M. Ca ...; Wojczynski, Mary ...; Frazier-Wood, Al ...; show more...; Houston, Denise ...; Kanoni, Stavroul ...; Lemaitre, Rozenn ...; Luan, Jian'an; Mikkila, Vera; Renström, Frida; Sonestedt, Emily; Zhao, Jing Hua; Chu, Audrey Y.; Qi, Lu; Chasman, Daniel ...; Otto, Marcia C. ...; Dhurandhar, Emil ...; Feitosa, Mary F.; Johansson, Ingeg ...; Khaw, Kay-Tee; Lohman, Kurt K.; Manichaikul, Ani; McKeown, Nicola ...; Mozaffarian, Dar ...; Singleton, Andre ...; Stirrups, Kathle ...; Viikari, Jorma; Ye, Zheng; Bandinelli, Stef ...; Barroso, Ines; Deloukas, Panos; Forouhi, Nita G.; Hofman, Albert; Liu, Yongmei; Lyytikainen, Leo ...; North, Kari E.; Dimitriou, Maria; Hallmans, Göran; Kahonen, Mika; Langenberg, Clau ...; Ordovas, Jose M.; Uitterlinden, An ...; Hu, Frank B.; Kalafati, Ioanna ...; Raitakari, Olli; Franco, Oscar H.; Johnson, Andrew; Emilsson, Valur; Schrack, Jennife ...; Semba, Richard D ...; Siscovick, David ...; Arnett, Donna K.; Borecki, Ingrid ...; Franks, Paul; Kritchevsky, Ste ...; Lehtimaki, Terho; Loos, Ruth J. F.; Orho-Melander, M ...; Rotter, Jerome I ...; Wareham, Nichola ...; Witteman, Jacque ...; Ferrucci, Luigi; Dedoussis, Georg ...; Cupples, L. Adri ...; Nettleton, Jenni ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Health Sciences; and Nutrition and Di ...

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