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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
  • Alexis 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
  • Ani Manichaikul
  • Ruifang Li-Gao
  • Marie Claude Vohl
  • Carol A. Wang
  • Frank J.A. van Rooij
  • Jean Shin
  • Markus Perola
Organisations
External organisations
  • Massachusetts General Hospital
  • Broad Institute
  • University of Cambridge
  • Boston University
  • University of North Carolina
  • Harokopio University
  • University of Washington
  • Washington University in St. Louis
  • Finnish National Institute for Health and Welfare
  • Johns Hopkins Bloomberg School of Public Health
  • University of Michigan
  • University of Copenhagen
  • University of Tartu
  • Imperial College London
  • Wake Forest University
  • Pennington Biomedical Research Center
  • Peking University
  • Leiden University Medical Centre
  • Laval University
  • Institute of Nutrition and Functional Foods, Canada
  • University of Texas
  • Erasmus University Medical Center
  • Queen Mary University
  • Brigham and Women's Hospital / Harvard Medical School
  • University of Tampere
  • Data Tecnica International
  • National Institute on Aging, United States
  • University of Virginia
  • Hospital for Sick Children, Toronto
  • Sigfried and Janet Weis Center for Research
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalMolecular Psychiatry
Publication statusE-pub ahead of print - 2018 Jul 9
Publication categoryResearch
Peer-reviewedYes