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PLoS One. 2014 Dec 31;9(12):e111156. doi: 10.1371/journal.pone.0111156. eCollection 2014.

No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

Author information

1
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
2
National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America; National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda, Maryland, United States of America; Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
3
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
4
Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
5
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy.
6
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
7
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
8
Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
9
Brown Foundation Institute of Molecular Medicine, Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
10
Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
11
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
12
Division of Population Health Sciences & Education, St George's, University of London, Cranmer Terrace, London, United Kingdom.
13
Department of Biological Psychology, VU University & EMGO+ institute, VU Medical Centre, Amsterdam, the Netherlands.
14
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Genomics Initiative (NGI)-Sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands.
15
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland; Folkhalsan Research Centre, Helsinki, Finland.
16
Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
17
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom.
18
INSERM UMR_S 1062, Aix-Marseille Université, Marseille, France.
19
Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States of America.
20
Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
21
Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom.
22
Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
23
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
24
Department of Prosthetic Dentistry, Gerostomatology and Dental Materials, University Medicine Greifswald, Greifswald, Germany.
25
Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden; Science for Life Laboratory, Karolinska Insitutet, Stockholm, Sweden.
26
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom; Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
27
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany; Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany.
28
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; ESC-Environmental Science Center, University of Augsburg, Augsburg, Germany.
29
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
30
Department of Biostatistics, Boston University, Boston, Massachusetts, United States of America.
31
Department of Haematology, Erasmus Medical Center, Rotterdam, the Netherlands.
32
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
33
Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
34
Department of Public Health, University of Split Medical School, Split, Croatia.
35
Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, Scotland, United Kingdom.
36
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
37
Robertson Center for Biostatistics, University of Glasgow, Glasgow, United Kingdom.
38
BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, United Kingdom.
39
Intramural Research Program, National Institute on Aging, Baltimore, Maryland, United States of America.
40
Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
41
Department of Cardiovascular Research, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
42
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
43
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
44
Department of Statistics, University of Auckland, Auckland, New Zealand.
45
Royal North Shore Hospital, University of Sydney, Sydney, Australia.
46
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Genomics Initiative (NGI)-Sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
47
Division of Preventive Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
48
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
49
Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
50
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
51
Intramural Research Program, National Institute on Aging, Baltimore, Maryland, United States of America; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
52
Leibniz-Institut für Arterioskleroseforschung an der Universität Münster, Münster, Germany.
53
Department of Internal Medicine II - Cardiology, University of Ulm Medical Center, Ulm, Germany.
54
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America.
55
Harvard Medical School, Boston, Massachusetts, United States of America; Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
56
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom.
57
Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom; Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, United Kingdom.
58
Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois, United States of America.
59
INSERM, UMR_S 1166, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France; ICAN Institute for Cardiometabolism and Nutrition, Paris, France.
60
Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
61
Folkhalsan Research Centre, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
62
Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom.
63
Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, United States of America.
64
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Durrer Center for Cardiogenetic Research, Amsterdam, the Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
65
Division of Preventive Medicine, Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
66
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
67
Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
68
National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America; National Heart, Lung and Blood Institute Division of Intramural Research, Bethesda, Maryland, United States of America.
69
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich, Munich, Germany.
70
Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland; Group Health Research Institute, Group Health Cooperative, Seattle, Washington, United States of America; Seattle Epidemiologic Research & Information Center, Veterans Affairs Office of Research & Development, Seattle, Washington, United States of America.

Abstract

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

PMID:
25551457
PMCID:
PMC4281156
DOI:
10.1371/journal.pone.0111156
[Indexed for MEDLINE]
Free PMC Article

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