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Get Free AccessMacronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10−6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.
José G. Merino, Hassan S. Dashti, S.X. Li, Chloé Sarnowski, Anne E. Justice, M. Graff, Constantina Papoutsakis, Caren E. Smith, George Dedoussis, Rozenn N. Lemaître, M.K. Wojczynski, S. Männistö, J.S. Ngwa, Minjung Kho, Tarunveer S. Ahluwalia, Natalia Pervjakova, Denise K. Houston, Claude Bouchard, Tao Huang, M. Orho-Melander, Alexis C. Wood, D.O. Mook-Kanamori, Louis Pérusse, C.E. Pennell, P.S. de Vries, Trudy Voortman, Li Ou, Stavroula Kanoni, L.M. Rose, T. Lehtimäki, Junsheng Zhao, M.F. Feitosa, Jia Luan, Nicola M. McKeown, J.A. Smith, T. Hansen, Niina Eklund, Michael A. Nalls, T. Rankinen, Jia Huang, D.G. Hernandez, C.-A. Schulz, A. Manichaikul, R. Li-Gao, Marie‐Claude Vohl, C.A. Wang, Frank J.A. van Rooij, Jean Shin, Ioanna Panagiota Kalafati, Felix R. Day, P.M. Ridker, M. Kähönen, David S. Siscovick, C. Langenberg, Wanting Zhao, Arne Astrup, Paul Knekt, Melissa Garcia, D. C. Rao, Q. Qi, L. Ferrucci, Ulrika Ericson, J. Blangero, A. Hofman, Zdenka Pausová, Vera Mikkilä, N.J. Wareham, S.L.R. Kardia, O. Pedersen, Antti Jula, Joanne E. Curran, M. Carola Zillikens, Jorma Viikari, Nita G. Forouhi, José M. Ordovás, John C. Lieske, Harri Rissanen, André G. Uitterlinden, O. T. Raitakari, Jessica C. Kiefte‐de Jong, Josée Dupuis, J.I. Rotter, K.E. North, Robert A. Scott, M.A. Province, Markus Perola, L. Adrienne Cupples, S.T. Turner, Thorkild I. A. Sørensen, V. Salomaa, Y. Liu, Yongjun Sung, Lu Qi, Stefania Bandinelli, Stephen S. Rich, R. de Mutsert, Angelo Tremblay, Wendy H. Oddy, O.H. Franco, Tomáš Paus (2019). Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium. Carolina Digital Repository (University of North Carolina at Chapel Hill), DOI: 10.17615/k873-hx84.
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Type
Article
Year
2019
Authors
100
Datasets
0
Total Files
0
Language
English
Journal
Carolina Digital Repository (University of North Carolina at Chapel Hill)
DOI
10.17615/k873-hx84
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