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dc.contributor.authorMerino, Jordien
dc.contributor.authorGuasch-Ferré, Martaen
dc.contributor.authorEllervik, Christinaen
dc.contributor.authorDashti, Hassan Sen
dc.contributor.authorSharp, Stephenen
dc.contributor.authorWu, Peitaoen
dc.contributor.authorOvervad, Kimen
dc.contributor.authorSarnowski, Chloéen
dc.contributor.authorKuokkanen, Mikkoen
dc.contributor.authorLemaitre, Rozenn Nen
dc.contributor.authorJustice, Anne Een
dc.contributor.authorEricson, Ulrikaen
dc.contributor.authorBraun, Kim VEen
dc.contributor.authorMahendran, Yuvarajen
dc.contributor.authorFrazier-Wood, Alexis Cen
dc.contributor.authorSun, Dianjianyien
dc.contributor.authorChu, Audrey Yen
dc.contributor.authorTanaka, Toshikoen
dc.contributor.authorLuan, Jian'anen
dc.contributor.authorHong, Jaeyoungen
dc.contributor.authorTjønneland, Anneen
dc.contributor.authorDing, Mingen
dc.contributor.authorLundqvist, Annamarien
dc.contributor.authorMukamal, Kennethen
dc.contributor.authorRohde, Rebeccaen
dc.contributor.authorSchulz, Christina-Alexandraen
dc.contributor.authorFranco, Oscar Hen
dc.contributor.authorGrarup, Nielsen
dc.contributor.authorChen, Yii-Der Idaen
dc.contributor.authorBazzano, Lydiaen
dc.contributor.authorFranks, Paul Wen
dc.contributor.authorBuring, Julie Een
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorLiu, Ching-Tien
dc.contributor.authorHansen, Torbenen
dc.contributor.authorJensen, Majken Ken
dc.contributor.authorSääksjärvi, Katrien
dc.contributor.authorPsaty, Bruce Men
dc.contributor.authorYoung, Kristin Len
dc.contributor.authorHindy, Georgeen
dc.contributor.authorSandholt, Camilla Heleneen
dc.contributor.authorRidker, Paul Men
dc.contributor.authorOrdovas, Jose Men
dc.contributor.authorMeigs, James Ben
dc.contributor.authorPedersen, Olufen
dc.contributor.authorKraft, Peteren
dc.contributor.authorPerola, Markusen
dc.contributor.authorNorth, Kari Een
dc.contributor.authorOrho-Melander, Marjuen
dc.contributor.authorVoortman, Trudyen
dc.contributor.authorToft, Ullaen
dc.contributor.authorRotter, Jerome Ien
dc.contributor.authorQi, Luen
dc.contributor.authorForouhi, Nitaen
dc.contributor.authorMozaffarian, Dariushen
dc.contributor.authorSørensen, Thorkild IAen
dc.contributor.authorStampfer, Meir Jen
dc.contributor.authorMännistö, Satuen
dc.contributor.authorSelvin, Elizabethen
dc.contributor.authorImamura, Fumiakien
dc.contributor.authorSalomaa, Veikkoen
dc.contributor.authorHu, Frank Ben
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorDupuis, Joséeen
dc.contributor.authorSmith, Caren Een
dc.contributor.authorKilpeläinen, Tuomas Oen
dc.contributor.authorChasman, Daniel Ien
dc.contributor.authorFlorez, Jose Cen
dc.description.abstractAbstract OBJECTIVE: To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes. DESIGN: Individual participant data meta-analysis. DATA SOURCES: Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators. REVIEW METHODS: Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score. RESULTS: Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I2=7.1%, τ2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I2=18.0%, τ2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, τ2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I2=25.9%, τ2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed. CONCLUSIONS: These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.
dc.description.sponsorshipThe EPIC-InterAct study received funding from the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Programme 6 of the European Community). We thank all EPIC participants and staff for their contribution to the study. We thank Nicola Kerrison (MRC Epidemiology Unit, University of Cambridge, Cambridge, UK) for managing the data for the InterAct Project. In addition, InterAct investigators acknowledge funding from the following agencies: MT: Health Research Fund (FIS) of the Spanish Ministry of Health; the CIBER en Epidemiología y Salud Pública (CIBERESP), Spain; Murcia Regional Government (N° 6236); JS: JS was supported by a Heisenberg-Professorship (SP716/2-1), a Clinical Research Group (KFO218/1) and a research group (Molecular Nutrition to JS) of the Bundesministerium für Bildung und Forschung (BMBF); YTvdS, JWJB, PHP, IS: Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; HBBdM: 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 (The Netherlands); MDCL: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (N° 6236); FLC: Cancer Research UK; PD: Wellcome Trust; LG: Swedish Research Council; GH: The county of Västerbotten; RK: Deutsche Krebshilfe; TJK: Cancer Research UK; KK: Medical Research Council UK, Cancer Research UK; AK: Medical Research Council (Cambridge Lipidomics Biomarker Research Initiative); CN: Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government (N° 6236); KO: Danish Cancer Society; OP: Faculty of Health Science, 47 University of Aarhus, Denmark; JRQ: Asturias Regional Government; LRS: Asturias Regional Government; AT: Danish Cancer Society; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; DLvdA, WMMV: 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 (The Netherlands); MMC: Wellcome Trust (083270/Z/07/Z), MRC (G0601261).
dc.rightsAttribution-NonCommercial 4.0 International
dc.subjectDiabetes Mellitus, Type 2en
dc.subjectDietary Fatsen
dc.subjectProportional Hazards Modelsen
dc.subjectRisk Factorsen
dc.subjectProspective Studiesen
dc.subjectMiddle Ageden
dc.subjectGenome-Wide Association Studyen
dc.titleQuality of dietary fat and genetic risk of type 2 diabetes: individual participant data meta-analysis.en
prism.publicationNameBMJ (Clinical research ed.)en
dc.contributor.orcidMerino, Jordi [0000-0001-8312-1438]
dc.contributor.orcidDashti, Hassan S [0000-0001-8525-1404]
dc.contributor.orcidSharp, Stephen [0000-0003-2375-1440]
dc.contributor.orcidOvervad, Kim [0000-0001-6429-7921]
dc.contributor.orcidKuokkanen, Mikko [0000-0003-4375-9327]
dc.contributor.orcidLuan, Jian'an [0000-0003-3137-6337]
dc.contributor.orcidTjønneland, Anne [0000-0003-4385-2097]
dc.contributor.orcidGrarup, Niels [0000-0001-5526-1070]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidHansen, Torben [0000-0001-8748-3831]
dc.contributor.orcidJensen, Majken K [0000-0003-4729-7545]
dc.contributor.orcidHindy, George [0000-0002-7257-9299]
dc.contributor.orcidPedersen, Oluf [0000-0002-3321-3972]
dc.contributor.orcidToft, Ulla [0000-0001-7770-8419]
dc.contributor.orcidForouhi, Nita [0000-0002-5041-248X]
dc.contributor.orcidImamura, Fumiaki [0000-0002-6841-8396]
dc.contributor.orcidHu, Frank B [0000-0002-6841-8396]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidKilpeläinen, Tuomas O [0000-0002-8349-3028]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
pubs.funder-project-idEuropean Commision (37197)

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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International