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.
Authors
Merino, Jordi
Dashti, Hassan S
Li, Sherly X
Sarnowski, Chloé
Justice, Anne E
Graff, Misa
Papoutsakis, Constantina
Smith, Caren E
Dedoussis, George V
Lemaitre, Rozenn N
Wojczynski, Mary K
Männistö, Satu
Ngwa, Julius S
Kho, Minjung
Ahluwalia, Tarunveer S
Pervjakova, Natalia
Houston, Denise K
Bouchard, Claude
Huang, Tao
Orho-Melander, Marju
Frazier-Wood, Alexis C
Mook-Kanamori, Dennis O
Pérusse, Louis
Pennell, Craig E
de Vries, Paul S
Voortman, Trudy
Li, Olivia
Kanoni, Stavroula
Rose, Lynda M
Lehtimäki, Terho
Feitosa, Mary F
McKeown, Nicola M
Smith, Jennifer A
Hansen, Torben
Eklund, Niina
Nalls, Mike A
Rankinen, Tuomo
Huang, Jinyan
Hernandez, Dena G
Schulz, Christina-Alexandra
Manichaikul, Ani
Li-Gao, Ruifang
Vohl, Marie-Claude
Wang, Carol A
van Rooij, Frank JA
Shin, Jean
Kalafati, Ioanna P
Ridker, Paul M
Kähönen, Mika
Siscovick, David S
Zhao, Wei
Astrup, Arne
Knekt, Paul
Garcia, Melissa
Rao, DC
Qi, Qibin
Ferrucci, Luigi
Ericson, Ulrika
Blangero, John
Hofman, Albert
Pausova, Zdenka
Mikkilä, Vera
Wareham, Nick J
Kardia, Sharon LR
Pedersen, Oluf
Jula, Antti
Curran, Joanne E
Zillikens, M Carola
Viikari, Jorma S
Forouhi, Nita G
Ordovás, José M
Lieske, John C
Rissanen, Harri
Uitterlinden, André G
Raitakari, Olli T
Kiefte-de Jong, Jessica C
Dupuis, Josée
Rotter, Jerome I
North, Kari E
Scott, Robert A
Province, Michael A
Perola, Markus
Cupples, L Adrienne
Turner, Stephen T
Sørensen, Thorkild IA
Salomaa, Veikko
Liu, Yongmei
Sung, Yun J
Qi, Lu
Bandinelli, Stefania
Rich, Stephen S
de Mutsert, Renée
Tremblay, Angelo
Oddy, Wendy H
Franco, Oscar H
Paus, Tomas
Florez, Jose C
Deloukas, Panos
Lyytikäinen, Leo-Pekka
Chasman, Daniel I
Chu, Audrey Y
Tanaka, Toshiko
Publication Date
2018-07-09Journal Title
Molecular Psychiatry
ISSN
1476-5578
Publisher
Springer Nature
Language
eng
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Merino, J., Dashti, H. S., Li, S. X., Sarnowski, C., Justice, A. E., Graff, M., Papoutsakis, C., et al. (2018). 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.. Molecular Psychiatry https://doi.org/10.1038/s41380-018-0079-4
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.
Sponsorship
Medical Research Council (MC_UU_12015/1)
MRC (MC_PC_13048)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Medical Research Council (MC_UU_12015/5)
Medical Research Council (MC_UU_12015/2)
Identifiers
External DOI: https://doi.org/10.1038/s41380-018-0079-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280348
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