| Literature DB >> 29988085 |
Jordi Merino1,2,3, Hassan S Dashti1,2, Daniel I Chasman4,5, Audrey Y Chu6, Toshiko Tanaka7, Sherly X Li8, Chloé Sarnowski9, Anne E Justice10,11, Misa Graff11, Constantina Papoutsakis12, Caren E Smith13, George V Dedoussis14, Rozenn N Lemaitre15, Mary K Wojczynski16, Satu Männistö17, Julius S Ngwa9,18, Minjung Kho19, Tarunveer S Ahluwalia20, Natalia Pervjakova17,21,22,23, Denise K Houston24, Claude Bouchard25, Tao Huang26, Marju Orho-Melander27, Alexis C Frazier-Wood28, Dennis O Mook-Kanamori29,30, Louis Pérusse31,32, Craig E Pennell33, Paul S de Vries34, Trudy Voortman35, Olivia Li36, Stavroula Kanoni37, Lynda M Rose6, Terho Lehtimäki4, Jing Hua Zhao8, Mary F Feitosa16, Jian'an Luan8, Nicola M McKeown38, Jennifer A Smith19, Torben Hansen20, Niina Eklund17, Mike A Nalls39,40, Tuomo Rankinen25, Jinyan Huang41, Dena G Hernandez40, Christina-Alexandra Schulz27, Ani Manichaikul42, Ruifang Li-Gao29, Marie-Claude Vohl32,43, Carol A Wang33, Frank J A van Rooij35, Jean Shin36, Ioanna P Kalafati14, Felix Day8, Paul M Ridker6,44, Mika Kähönen4, David S Siscovick45, Claudia Langenberg8, Wei Zhao19, Arne Astrup46, Paul Knekt17, Melissa Garcia47, D C Rao48, Qibin Qi49, Luigi Ferrucci50, Ulrika Ericson27, John Blangero51, Albert Hofman35,52, Zdenka Pausova36,53, Vera Mikkilä54, Nick J Wareham8, Sharon L R Kardia19, Oluf Pedersen20, Antti Jula17, Joanne E Curran51, M Carola Zillikens55, Jorma S Viikari56,57, Nita G Forouhi8, José M Ordovás13,58,59, John C Lieske60, Harri Rissanen17, André G Uitterlinden35,55, Olli T Raitakari61,62, Jessica C Kiefte-de Jong35,63, Josée Dupuis9, Jerome I Rotter64,65, Kari E North11,66, Robert A Scott8, Michael A Province16, Markus Perola17, L Adrienne Cupples9,67, Stephen T Turner60, Thorkild I A Sørensen20,68, Veikko Salomaa17, Yongmei Liu69, Yun J Sung48, Lu Qi70, Stefania Bandinelli71, Stephen S Rich72, Renée de Mutsert29, Angelo Tremblay31, Wendy H Oddy73,74, Oscar H Franco35, Tomas Paus75,76,77, Jose C Florez1,2,3, Panos Deloukas37,78, Leo-Pekka Lyytikäinen4.
Abstract
Macronutrient 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.Entities:
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Year: 2018 PMID： 29988085 PMCID： PMC6326896 DOI： 10.1038/s41380-018-0079-4
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 15.992