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PMID: 29988085 Published · ppublish English

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 ·Vol. 24 ·No. 12 ·2019-00-00

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

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.

Article Info
Journal
Molecular psychiatry
Abbr.
Mol Psychiatry
ISSN
1476-5578
Corresponding email
Published
2019-00-00
Language
English
Country/Region
England
NLM ID
9607835
Analysis Services
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