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-Melander; 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; 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

doi:10.1038/s41380-018-0079-4

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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

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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, …

Molecular psychiatry, Vol.24(12), pp.1920-1932

01/12/2019

DOI: https://doi.org/10.1038/s41380-018-0079-4

PMCID: PMC6326896

PMID: 29988085

Abstract

Aged

Aging - genetics

Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics

Cohort Studies

Energy Intake - genetics

European Continental Ancestry Group - genetics

Female

Fibroblast Growth Factors - genetics

Genetic Loci - genetics

Genetic Predisposition to Disease - epidemiology

Genetic Predisposition to Disease - genetics

Genome-Wide Association Study

Genomics - methods

Genotype

Heart Diseases - epidemiology

Heart Diseases - genetics

Humans

Male

Membrane Proteins - genetics

Middle Aged

Nutrients

Obesity - genetics

Polymorphism, Single Nucleotide - genetics

Receptors, Retinoic Acid - genetics

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 ) 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.

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Title: 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
Creators - without role: Jordi Merino - Massachusetts General Hospital
Hassan S Dashti - Massachusetts General Hospital
Sherly X Li - University of Cambridge
Chloé Sarnowski - Boston University
Anne E Justice - University of North Carolina at Chapel Hill
Misa Graff - University of North Carolina at Chapel Hill
Constantina Papoutsakis - Academy of Nutrition and Dietetics
Caren E Smith - Tufts University
George V Dedoussis - Harokopio University of Athens
Rozenn N Lemaitre - University of Washington
Mary K Wojczynski - Washington University in St. Louis
Satu Männistö - Finnish Institute for Health and Welfare
Julius S Ngwa - Boston University
Minjung Kho - University of Michigan–Ann Arbor
Tarunveer S Ahluwalia - Novo Nordisk Foundation
Natalia Pervjakova - University of Tartu
Denise K Houston - Wake Forest University
Claude Bouchard - Pennington Biomedical Research Center
Tao Huang - Peking University
Marju Orho-Melander - Lund University
Alexis C Frazier-Wood - Children's Nutrition Research Center at Baylor College of Medicine
Dennis O Mook-Kanamori - Leiden University Medical Center
Louis Pérusse - Université Laval
Craig E Pennell - University of Newcastle Australia
Paul S de Vries - The University of Texas Health Science Center at Houston
Trudy Voortman - Erasmus MC
Olivia Li - University of Toronto
Stavroula Kanoni - Queen Mary University of London
Lynda M Rose - Brigham and Women's Hospital
Terho Lehtimäki - Tampere University
Jing Hua Zhao - MRC Epidemiology Unit
Mary F Feitosa - Washington University in St. Louis
Jian'an Luan - University of Cambridge
Nicola M McKeown - Tufts University
Jennifer A Smith - University of Michigan–Ann Arbor
Torben Hansen - Novo Nordisk Foundation
Niina Eklund - Finnish Institute for Health and Welfare
Mike A Nalls - National Institute on Aging
Tuomo Rankinen - Pennington Biomedical Research Center
Jinyan Huang - Shanghai Institute of Hematology
Dena G Hernandez - National Institute on Aging
Christina-Alexandra Schulz - Lund University
Ani Manichaikul - University of Virginia
Ruifang Li-Gao - Leiden University Medical Center
Marie-Claude Vohl - Université Laval
Carol A Wang - University of Newcastle Australia
Frank J A van Rooij - Erasmus MC
Jean Shin - University of Toronto
Ioanna P Kalafati - Harokopio University of Athens
Felix Day - MRC Epidemiology Unit
Paul M Ridker - Brigham and Women's Hospital
Mika Kähönen - Tampere University
David S Siscovick - New York Academy of Medicine
Claudia Langenberg - University of Cambridge
Wei Zhao - University of Michigan–Ann Arbor
Arne Astrup - University of Copenhagen
Paul Knekt - Finnish Institute for Health and Welfare
Melissa Garcia - National Institute on Aging
D C Rao - Washington University in St. Louis
Qibin Qi - Albert Einstein College of Medicine
Luigi Ferrucci - National Institute on Aging
Ulrika Ericson - Lund University
John Blangero - The University of Texas Rio Grande Valley
Albert Hofman - Erasmus MC
Zdenka Pausova - University of Toronto
Vera Mikkilä - Department of Food and Environmental Sciences, Division of Nutrition, Helsinki, Finland
Nick J Wareham - University of Cambridge
Sharon L R Kardia - University of Michigan–Ann Arbor
Oluf Pedersen - University of Copenhagen
Antti Jula - Finnish Institute for Health and Welfare
Joanne E Curran - The University of Texas Rio Grande Valley
M Carola Zillikens - Erasmus MC
Jorma S Viikari - University of Turku
Nita G Forouhi - University of Cambridge
José M Ordovás - Tufts University
John C Lieske - Mayo Clinic
Harri Rissanen - Finnish Institute for Health and Welfare
André G Uitterlinden - Erasmus MC
Olli T Raitakari - University of Turku
Jessica C Kiefte-de Jong - Leiden University
Josée Dupuis - Boston University
Jerome I Rotter - Harbor–UCLA Medical Center
Kari E North - University of North Carolina at Chapel Hill
Robert A Scott - University of Cambridge
Michael A Province - Washington University in St. Louis
Markus Perola - Finnish Institute for Health and Welfare
L Adrienne Cupples - Framingham Heart Study
Stephen T Turner - Mayo Clinic
Thorkild I A Sørensen - Novo Nordisk Foundation
Veikko Salomaa - Finnish Institute for Health and Welfare
Yongmei Liu - Wake Forest University
Yun J Sung - Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
Lu Qi - Tulane University
Stefania Bandinelli - Azienda Sanitaria di Firenze
Stephen S Rich - University of Virginia
Renée de Mutsert - Leiden University Medical Center
Angelo Tremblay - Université Laval
Wendy H Oddy - Telethon Kids Institute
Oscar H Franco - Erasmus MC
Tomas Paus - University of Toronto
Jose C Florez - Massachusetts General Hospital
Panos Deloukas - King Abdulaziz University
Leo-Pekka Lyytikäinen - University of Tampere
Daniel I Chasman - Brigham and Women's Hospital
Audrey Y Chu - Brigham and Women's Hospital
Toshiko Tanaka - National Institute on Aging
Publication Details: Molecular psychiatry, Vol.24(12), pp.1920-1932
Grant note: MC_UU_12015/1 / Medical Research Council MC_UU_12015/5 / Medical Research Council K24 DK110550 / NIDDK NIH HHS MC_UU_12015/2 / Medical Research Council R01 HL105756 / NHLBI NIH HHS MC_QA137853 / Medical Research Council R01 HL119443 / NHLBI NIH HHS U01 CA182913 / NCI NIH HHS N01 HC025195 / NHLBI NIH HHS MC_PC_17228 / Medical Research Council T32 HL007055 / NHLBI NIH HHS K08 HL112845 / NHLBI NIH HHS T32 EY022303 / NEI NIH HHS RG/14/5/30893 / British Heart Foundation U01 AG023746 / NIA NIH HHS
Identifiers: 9938794208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article