A1 Refereed original research article in a scientific journal
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 J, Dashti HS, Li SX, Sarnowski C, Justice AE, Graff M, Papoutsakis C, Smith CE, Dedoussis GV, Lemaitre RN, Wojczynski MK, Männistö S, Ngwa JS, Kho M, Ahluwalia TS, Pervjakova N, Houston DK, Bouchard C, Huang T, Orho-Melander M, Frazier-Wood AC, Mook-Kanamori DO, Pérusse L, Pennell CE, de Vries PS, Voortman T, Li O, Kanoni S, Rose LM, Lehtimäki T, Zhao JH, Feitosa MF, Luan J, McKeown NM, Smith JA, Hansen T, Eklund N, Nalls MA, Rankinen T, Huang J, Hernandez DG, Schulz CA, Manichaikul A, Li-Gao R, Vohl MC, Wang CA, van Rooij FJA, Shin J, Kalafati IP, Day F, Ridker PM, Kähönen M, Siscovick DS, Langenberg C, Zhao W, Astrup A, Knekt P, Garcia M, Rao DC, Qi Q, Ferrucci L, Ericson U, Blangero J, Hofman A, Pausova Z, Mikkilä V, Wareham NJ, Kardia SLR, Pedersen O, Jula A, Curran JE, Zillikens MC, Viikari JS, Forouhi NG, Ordovás JM, Lieske JC, Rissanen H, Uitterlinden AG, Raitakari OT, Kiefte-de Jong JC, Dupuis J, Rotter JI, North KE, Scott RA, Province MA, Perola M, Cupples LA, Turner ST, Sørensen TIA, Salomaa V, Liu Y, Sung YJ, Qi L, Bandinelli S, Rich SS, de Mutsert R, Tremblay A, Oddy WH, Franco OH, Paus T, Florez JC, Deloukas P, Lyytikäinen LP, Chasman DI, Chu AY, Tanaka T
Publication year: 2019
Journal: Molecular Psychiatry
Volume: 24
Issue: 12
First page : 1920
Last page: 1932
Number of pages: 13
ISSN: 1359-4184
DOI: https://doi.org/10.1038/s41380-018-0079-4
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.
