Format

Send to

Choose Destination
Hum Mol Genet. 2015 Aug 15;24(16):4728-38. doi: 10.1093/hmg/ddv186. Epub 2015 May 20.

Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

Author information

1
Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas, Health Science Center, Houston, TX, USA.
2
Department of Mathematics, University of St. Thomas, Houston, TX, USA.
3
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
4
Jean Mayer USDA Human Nutrition Research Center on Aging, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
5
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit.
6
Clinical Research Branch, National Institute on Aging, Baltimore, MD, USA.
7
Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
8
Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.
9
Department of Medicine, University of Washington, Seattle, WA, USA.
10
Unit of Public Health Genomics.
11
Unit of Public Health Genomics, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, Helsinki 00290, Finland.
12
Department of Internal Medicine.
13
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Haartmaninkatu 8, Helsinki 00290, Finland.
14
Department of Nutrition, Harvard Chan School of Public Health, Boston, MA, USA, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
15
Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden.
16
Center for Public Health Genomics, Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
17
William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
18
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
19
Department of Food and Environmental Sciences, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
20
Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.
21
The New York Academy of Medicine, New York, NY, USA.
22
THL-National Institute for Health and Welfare, Mannerheimintie 166, Helsinki 00300, Finland.
23
Department of Odontology.
24
Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, NC, USA.
25
Institute of Behavioral Sciences, Folkhälsan Research Centre, Helsinki, Finland.
26
Department of Nutrition, Harvard Chan School of Public Health, Boston, MA, USA.
27
Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
28
Center for Public Health Genomics.
29
Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
30
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
31
Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
32
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland, Department of Clinical Physiology and Nuclear Medicine.
33
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
34
Department of Public Health and Clinical Medicine, Nutritional Research.
35
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
36
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
37
Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
38
Division of Aging, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA, Harvard Medical School and Boston VA Healthcare System, Boston, MA, USA.
39
Unit of Public Health Genomics, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, Helsinki 00290, Finland, University of Tartu, Estonian Genome Center, Ülikooli 18, Tartu 50090, Estonia.
40
Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, UK, University of Cambridge Metabolic Research Labs, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
41
Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.
42
Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
43
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Haartmaninkatu 8, Helsinki 00290, Finland, Folkhälsan Research Centre, Helsinki, Finland, Department of General Practice and Primary Health Care, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland, Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
44
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
45
Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
46
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Department of Biobank Research.
47
The Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine and The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
48
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Department of Nutrition, Harvard Chan School of Public Health, Boston, MA, USA, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden, paul.franks@med.lu.se.

Abstract

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

PMID:
25994509
PMCID:
PMC4512626
DOI:
10.1093/hmg/ddv186
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Grant support

Publication types

MeSH terms

Grant support

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center