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Mol Psychiatry. 2018 Jul 9. doi: 10.1038/s41380-018-0079-4. [Epub ahead of print]

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.

Author information

1
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
2
Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
3
Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
4
MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
5
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
6
Biomedical and Translational Informatics Institute, Geisinger Health Weis Center for Research, Danvilla, PA, USA.
7
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
8
Research International and Scientific Affairs, Academy of Nutrition and Dietetics, Chicago, IL, USA.
9
Nutrition and Genomics, JM-USDA-HNRCA at Tufts University, Boston, MA, USA.
10
Department of Dietetics and Nutritional Science, School of Health Science and Education, Harokopio University, Athens, Greece.
11
Departments of Medicine, University of Washington, Seattle, USA.
12
Department of Genetics, Washington University School of Medicine, Saint Louis, MO, USA.
13
National Institute for Health and Welfare, Helsinki, Finland.
14
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
15
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
16
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
17
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
18
Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
19
Genomics of Common Disease, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, UK.
20
Department of Internal Medicine, Wake Forest School of Medicine, Winston Salem, NC, USA.
21
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
22
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Peking, China.
23
Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden.
24
USDA/ARS Children's Nutrition Research Center, Houston, TX, USA.
25
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
26
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
27
Department of Kinesiology, Faculty of Medicine, Laval University, Québec, Canada.
28
Institute of Nutrition and Functional Foods, Québec, Canada.
29
School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Callaghan, Australia.
30
Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
31
Department of Epidemiology, Erasmus MC University Hospital, Rotterdam, The Netherlands.
32
The Hospital for Sick Children, Translational Medicine, University of Toronto, Toronto, Canada.
33
William Harvey Research Institute, Queen Mary University of London, London, UK.
34
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
35
Department of Clinical Chemistry, Fimlab Laboratories, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
36
Nutritional Epidemiology, JM-USDA-HNRCA at Tufts University, Boston, MA, USA.
37
Data Tecnica International, Glen Echo, MD, USA.
38
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
39
Department of Bioinformatics, Shanghai Institute of Hematology, Shanghai, China.
40
Center for Public Health Genomics, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
41
School of Nutrition, Laval University, Québec, Canada.
42
Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
43
New York Academy of Medicine, New York, NY, USA.
44
Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
45
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
46
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
47
Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
48
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
49
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA.
50
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
51
Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada.
52
Department of Food and Environmental Sciences, Division of Nutrition, Helsinki, Finland.
53
Department of Internal Medicine, Erasmus MC University Hospital, Rotterdam, The Netherlands.
54
Division of Medicine, Turku University Hospital, Turku, Finland.
55
Department of Medicine, University of Turku, Turku, Finland.
56
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
57
IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
58
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
59
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
60
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
61
Global Public Health, Leiden University College, The Hague, The Netherlands.
62
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
63
Departments of Pediatrics and Medicine, Division of Genomic Outcomes, Harbor-UCLA Medical Center, Torrance, CA, USA.
64
Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.
65
NHLBI Framingham Heart Study, Framingham, MA, USA.
66
Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
67
Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, NC, USA.
68
Department of Epidemiology, Tulane University, New Orleans, LA, USA.
69
Geriatric Unit, Azienda Sanitaria Firenze-ASF, Florence, Italy.
70
Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
71
Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.
72
Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia.
73
Rotman Research Institute, University of Toronto, Toronto, Canada.
74
Department of Psychiatry and Psychology, University of Toronto, Toronto, Canada.
75
Child Mind Institute, New York, NY, USA.
76
Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
77
Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
78
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA. tanakato@mail.nih.gov.

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.

PMID:
29988085
DOI:
10.1038/s41380-018-0079-4

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