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

Jordi Merino, Hassan S. Dashti, Sherly X. Li, Chloé Sarnowski, Anne E. Justice, Misa Graff, Constantina Papoutsakis, Caren E. Smith, George V. Dedoussis, Rozenn N. Lemaitre, Mary K. Wojczynski, Satu Männistö, Julius S. Ngwa, Minjung Kho, Tarunveer S. Ahluwalia, Natalia Pervjakova, Denise K. Houston, Claude Bouchard, Tao Huang, Marju Orho-MelanderAlexis C. Frazier-Wood, Dennis O. Mook-Kanamori, Louis Pérusse, Craig E. Pennell, Paul S. de Vries, Trudy Voortman, Olivia Li, Stavroula Kanoni, Lynda M. Rose, Terho Lehtimäki, Jing Hua Zhao, Mary F. Feitosa, Jian’an Luan, Nicola M. McKeown, Jennifer A. Smith, Torben Hansen, Niina Eklund, Mike A. Nalls, Tuomo Rankinen, Jinyan Huang, Dena G. Hernandez, Christina Alexandra Schulz, Ani Manichaikul, Ruifang Li-Gao, Marie Claude Vohl, Carol A. Wang, Frank J.A. van Rooij, Jean Shin, Ioanna P. Kalafati, Felix Day, Paul M. Ridker, Mika Kähönen, David S. Siscovick, Claudia Langenberg, Wei Zhao, Arne Astrup, Paul Knekt, Melissa Garcia, D. C. Rao, Qibin Qi, Luigi Ferrucci, Ulrika Ericson, John Blangero, Albert Hofman, Zdenka Pausova, Vera Mikkilä, Nick J. Wareham, Sharon L.R. Kardia, Oluf Pedersen, Antti Jula, Joanne E. Curran, M. Carola Zillikens, Jorma S. Viikari, Nita G. Forouhi, José M. Ordovás, John C. Lieske, Harri Rissanen, André G. Uitterlinden, Olli T. Raitakari, Jessica C. Kiefte-de Jong, Josée Dupuis, Jerome I. Rotter, Kari E. North, Robert A. Scott, Michael A. Province, Markus Perola, L. Adrienne Cupples, Stephen T. Turner, Thorkild I.A. Sørensen, Veikko Salomaa, Yongmei Liu, Yun J. Sung, Lu Qi, Stefania Bandinelli, Stephen S. Rich, Renée de Mutsert, Angelo Tremblay, Wendy H. Oddy, Oscar H. Franco, Tomas Paus, Jose C. Florez, Panos Deloukas, Leo Pekka Lyytikäinen, Daniel I. Chasman, Audrey Y. Chu, Toshiko Tanaka

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1920-1932
Number of pages13
JournalMolecular Psychiatry
Issue number12
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Molecular Biology


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