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Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

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dc.contributor.authorLangenberg, Claudia
dc.contributor.authorSharp, Stephen J
dc.contributor.authorFranks, Paul W
dc.contributor.authorScott, Robert A
dc.contributor.authorDeloukas, Panos
dc.contributor.authorForouhi, Nita G
dc.contributor.authorFroguel, Philippe
dc.contributor.authorGroop, Leif C
dc.contributor.authorHansen, Torben
dc.contributor.authorPalla, Luigi
dc.contributor.authorPedersen, Oluf
dc.contributor.authorSchulze, Matthias B
dc.contributor.authorTormo, Maria-Jose
dc.contributor.authorWheeler, Eleanor
dc.contributor.authorAgnoli, Claudia
dc.contributor.authorArriola, Larraitz
dc.contributor.authorBarricarte, Aurelio
dc.contributor.authorBoeing, Heiner
dc.contributor.authorClarke, Geraldine M
dc.contributor.authorClavel-Chapelon, Françoise
dc.contributor.authorDuell, Eric J
dc.contributor.authorFagherazzi, Guy
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorKerrison, Nicola D
dc.contributor.authorKey, Timothy J
dc.contributor.authorKhaw, Kay Tee
dc.contributor.authorKröger, Janine
dc.contributor.authorLajous, Martin
dc.contributor.authorMorris, Andrew P
dc.contributor.authorNavarro, Carmen
dc.contributor.authorNilsson, Peter M
dc.contributor.authorOvervad, Kim
dc.contributor.authorPalli, Domenico
dc.contributor.authorPanico, Salvatore
dc.contributor.authorQuirós, J Ramón
dc.contributor.authorRolandsson, Olov
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorSanchez-Perez, Maria-Jose
dc.contributor.authorSlimani, Nadia
dc.contributor.authorSpijkerman, Annemieke M W
dc.contributor.authorTumino, Rosario
dc.contributor.authorvan der A, Daphne L
dc.contributor.authorvan der Schouw, Yvonne T
dc.contributor.authorBarroso, Inês
dc.contributor.authorMcCarthy, Mark I
dc.contributor.authorRiboli, Elio
dc.contributor.authorWareham, Nicholas J
dc.contributor.authoraffiliation[Langenberg,C; Sharp,SJ; Scott,RA; Forouhi,NG; Palla,L; Kerrison,ND; Wareham,NJ] Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. [Franks,PW; Nilsson,PM; Lund University, Malmö, Sweden. [Franks,PW; Rolandsson,O] Umea University, Umea, Sweden. [Deloukas,P; Wheeler,E; Barroso,I] The Wellcome Trust Sanger Institute, Cambridge, United Kingdom. [Froguel,P] Imperial College London, London, United Kingdom. [Groop,LC] University Hospital Scania, Malmö, Sweden. [Groop,LC] Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. [Hansen,T; Pedersen,O] The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Hansen,T] Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. [Pedersen,O] Faculty of Health Science, University of Aarhus, Aarhus, Denmark. [Pedersen,O] Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. [Schulze,MB; Boeing,H; Kröger,J] German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. [Tormo,M; Navarro,C] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Tormo,M; Arriola,L; Barricarte,A; Navarro,C; Sánchez, M] Consorcio de Investigación Biomédica de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Spain. [Tormo,M] Department of Health and Social Sciences, Universidad de Murcia, Spain. [Agnoli,C] Epidemiology and Prevention Unit, Milan, Italy. [Arriola,L] Public Health Division of Gipuzkoa, San Sebastian, Spain. [Arriola,L] Instituto de Investigación Sanitaria BioDonostia, Basque Government, San Sebastian, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Clarke,GM; Morris,AP; McCarthy,MI] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. [Clavel-Chapelon,F; Fagherazzi,G; Lajous,M] Inserm, Villejuif, France. [Clavel-Chapelon,F; Fagherazzi,G] Université Paris-Sud, Villejuif, France. [Duel,EJ] Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain. [Kaaks,R] German Cancer Research Center, Heidelberg, Germany. [Key,TJ] University of Oxford, Oxford, United Kingdom. [Khaw,KT] University of Cambridge, Cambridge, United Kingdom. [Lajous,M] Center for Research on Population Health, National Institute of Public Health of Mexico, Cuernavaca, Mexico. [Lajous,M] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. [Navarro,C] Unit of Preventive Medicine and Public Health, School of Medicine, University of Murcia, Murcia, Spain. [Overvad,K] Department of Public Health, Aarhus University, Aarhus, Denmark. Aalborg University Hospital, Aalborg, Denmark. [Palli,D] Cancer Research and Prevention Institute, Florence, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Sacerdote,C] Unit of Cancer Epidemiology, Azienda Ospedaliero Universitaria Citta` della Salute e della Scienza, University of Turin, Turin, Italy. Piedmont Reference Center for Epidemiology and Cancer Prevention, Torino, Italy. Human Genetics Foundation, Torino, Italy. [Sánchez,M] Andalusian School of Public Health, Granada, Spain. [Slimani,N] International Agency for Research on Cancer, Lyon, France. [Spijkerman,MW; A,DL] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. [Tumino,R] Azienda Sanitaria Provinciale di Ragusa, Ragusa, Italy. Azienda Sanitaria Provinciale di Ragusa, Ragusa, Italy. [Schouw,YT] University Medical Center Utrecht, Utrecht, The Netherlands. [Barroso,I] University of Cambridge Metabolic Research Laboratories, Cambridge, United Kingdom. [McCarthy,MI] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, United Kingdom. [McCarthy,MI] NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom. [Riboli,E] School of Public Health, Imperial College London, London, United Kingdom.es
dc.contributor.funderFunding: No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following agencies: PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; PD: Work was supported by the Wellcome Trust; LCG: Swedish Research Council; MJT: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (Nu 6236); LA: EJD: The Spanish Ministry of Health – ISCII RETICC RD06/0020; RK: German Cancer Aid, German Ministry of Research (BMBF); TJK: Cancer Research UK; KTK: Medical Research Council UK, Cancer Research UK; APM: Wellcome Trust grant numbers WT098017 and WT090532; CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (Nu 6236); PMN: Swedish Research Council; KO: Danish Cancer Society; SP: Compagnia di San Paolo; JRQ: Asturias Regional Government; OR: The Va¨sterboten County Council; AMWS and DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; YTvdS: Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; IB: Wellcome Trust grant 098051 and United Kingdom NIHR Cambridge Biomedical Research Centre; MIM: InterAct, Wellcome Trust (083270/Z/07/Z), MRC (G0601261); ER: Imperial College Biomedical Research Centre.
dc.date.accessioned2015-01-23T12:05:37Z
dc.date.available2015-01-23T12:05:37Z
dc.date.issued2014-05-20
dc.descriptionJournal Article; Research Support, Non-U.S. Gov't;es
dc.description.abstractBACKGROUND Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10-3) and waist circumference (p for interaction  = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.es
dc.description.versionYeses
dc.identifier.citationLangenberg C, Sharp SJ, Franks PW, Scott RA, Deloukas P, Forouhi NG, et al. Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. PLoS Med.. 2014 ; 11(5):e1001647es
dc.identifier.doi10.1371/journal.pmed.1001647
dc.identifier.essn1549-1676
dc.identifier.issn1549-1277
dc.identifier.pmcPMC4028183
dc.identifier.pmid24845081
dc.identifier.urihttp://hdl.handle.net/10668/1797
dc.journal.titlePLoS medicine
dc.language.isoen
dc.publisherPublic Library of Sciencees
dc.relation.publisherversionhttp://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001647es
dc.rights.accessRightsopen access
dc.subjectAleloses
dc.subjectÍndice de Masa Corporales
dc.subjectEstudios de Cohorteses
dc.subjectDiabetes Mellitus Tipo 2es
dc.subjectDieta Mediterráneaes
dc.subjectFemeninoes
dc.subjectPredisposición Genética a la Enfermedades
dc.subjectHumanoses
dc.subjectEstilo de Vidaes
dc.subjectMasculinoes
dc.subjectMediana Edades
dc.subjectActividad Motoraes
dc.subjectPolimorfismo de Nucleótido Simplees
dc.subjectModelos de Riesgos Proporcionaleses
dc.subjectFactores de Riesgoes
dc.subjectCircunferencia de la Cinturaes
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleleses
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Indexes
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studieses
dc.subject.meshMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2es
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Mediterraneanes
dc.subject.meshMedical Subject Headings::Check Tags::Femalees
dc.subject.meshMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Diseasees
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses
dc.subject.meshMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Stylees
dc.subject.meshMedical Subject Headings::Check Tags::Malees
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Agedes
dc.subject.meshMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activityes
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotidees
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards Modelses
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factorses
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size::Waist Circumferencees
dc.titleGene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.es
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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