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Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake.
Thursday,2013-12-05 10:03 America/Los_Angeles — poolea2
| Title | Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Tanaka, T, Ngwa, JS, van Rooij, FJA, Zillikens, CM, Wojczynski, MK, Frazier-Wood, AC, Houston, DK, Kanoni, S, Lemaitre, RN, Luan, J'an, Mikkilä, V, Renstrom, F, Sonestedt, E, Zhao, JH, Chu, AY, Qi, L, Chasman, DI, Otto, MC de Olive, Dhurandhar, EJ, Feitosa, MF, Johansson, I, Khaw, K-T, Lohman, KK, Manichaikul, A, McKeown, NM, Mozaffarian, D, Singleton, A, Stirrups, K, Viikari, J, Ye, Z, Bandinelli, S, Barroso, I, Deloukas, P, Forouhi, NG, Hofman, A, Liu, Y, Lyytikäinen, L-P, North, KE, Dimitriou, M, Hallmans, G, Kähönen, M, Langenberg, C, Ordovas, JM, Uitterlinden, AG, Hu, FB, Kalafati, I-P, Raitakari, O, Franco, OH, Johnson, A, Emilsson, V, Schrack, JA, Semba, RD, Siscovick, DS, Arnett, DK, Borecki, IB, Franks, PW, Kritchevsky, SB, Lehtimäki, T, Loos, RJF, Orho-Melander, M, Rotter, JI, Wareham, NJ, Witteman, JCM, Ferrucci, L, Dedoussis, G, Cupples, AL, Nettleton, JA |
| Journal | Am J Clin Nutr |
| Volume | 97 |
| Issue | 6 |
| Pagination | 1395-402 |
| Date Published | 2013 Jun |
| ISSN | 1938-3207 |
| Keywords | Alleles, Atherosclerosis, Body Mass Index, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Energy Intake, European Continental Ancestry Group, Fibroblast Growth Factors, Follow-Up Studies, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Life Style, Obesity, Polymorphism, Single Nucleotide, Prospective Studies, Quantitative Trait Loci, Surveys and Questionnaires |
| Abstract | <p><b>BACKGROUND: </b>Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants.</p><p><b>OBJECTIVE: </b>The objective of the study was to identify common genetic variants that are associated with macronutrient intake.</p><p><b>DESIGN: </b>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.</p><p><b>RESULTS: </b>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)).</p><p><b>CONCLUSION: </b>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).</p> |
| DOI | 10.3945/ajcn.112.052183 |
| Alternate Journal | Am. J. Clin. Nutr. |
| PubMed ID | 23636237 |
| PubMed Central ID | PMC3652928 |
| Grant List | R01 AG027012 / AG / NIA NIH HHS / United States MC_UP_A100_1003 / / Medical Research Council / United Kingdom R01 HL091357 / HL / NHLBI NIH HHS / United States / / Medical Research Council / United Kingdom T32 HL007575 / HL / NHLBI NIH HHS / United States R01 DK091718 / DK / NIDDK NIH HHS / United States G1000143 / / Medical Research Council / United Kingdom UL1 TR000124 / TR / NCATS NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States MC_U106179471 / / Medical Research Council / United Kingdom P30 DK063491 / DK / NIDDK NIH HHS / United States U01 HL072524 / HL / NHLBI NIH HHS / United States / / Canadian Institutes of Health Research / Canada 14136 / / Cancer Research UK / United Kingdom / / Cancer Research UK / United Kingdom G0401527 / / Medical Research Council / United Kingdom MC_UU_12015/5 / / Medical Research Council / United Kingdom MC_U106188470 / / Medical Research Council / United Kingdom R01 HL087700 / HL / NHLBI NIH HHS / United States / / Wellcome Trust / United Kingdom |