Linda E T Vissers1, Ivonne Sluijs2, Yvonne T van der Schouw1, Nita G Forouhi3, Fumiaki Imamura3, Stephen Burgess4, Aurelio Barricarte5, Heiner Boeing6, Catalina Bonet7, Maria-Dolores Chirlaque8,9, Guy Fagherazzi10, Paul W Franks11, Heinz Freisling12, Marc J Gunter12, J Ramón Quirós13, Daniel B Ibsen14, Rudolf Kaaks15, Timothy Key16, Kay T Khaw4, Tilman Kühn15, Olatz Mokoroa9,17, Peter M Nilsson11, Kim Overvad18, Valeria Pala19, Domenico Palli20, Salvatore Panico21, Carlotta Sacerdote22, Annemieke M W Spijkerman23, Anne Tjonneland24, Rosario Tumino25, Miguel Rodríguez-Barranco9,26, Olov Rolandsson27, Elio Riboli28, Stephen J Sharp3, Claudia Langenberg3, Nicholas J Wareham3. 1. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands i.sluijs-2@umcutrecht.nl. 3. MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K. 4. Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, U.K. 5. Navarre Public Health Institute (ISPN), Pamplona, Spain. 6. German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 7. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia, Barcelona, Spain. 8. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, University of Murcia, Murcia, Spain. 9. CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain. 10. Centre for Research in Epidemiology and Population Health (CESP), UMR1018, INSERM, Institut Gustave Roussy, Paris South University-Paris-Saclay University, Villejuif, France. 11. Lund University, Malmö, Sweden. 12. Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. 13. Public Health Directorate, Asturias, Spain. 14. Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. 15. German Cancer Research Center (DKFZ), Heidelberg, Germany. 16. University of Oxford, Oxford, U.K. 17. Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain. 18. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. 19. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 20. Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy. 21. Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. 22. Unit of Cancer Epidemiology, University Hospital "Città della Salute e della Scienza," University of Turin, and Center for Cancer Prevention (CPO), Torino, Italy. 23. National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. 24. Danish Cancer Society Research Center, Copenhagen, Denmark. 25. Azienda Sanitaria Provinciale (ASP) Ragusa, Ragusa, Italy. 26. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada, Universidad de Granada, Granada, Spain. 27. Umeå University, Umeå, Sweden. 28. School of Public Health, Imperial College London, London, U.K.
Abstract
OBJECTIVE: To estimate the causal association between intake of dairy products and incident type 2 diabetes. RESEARCH DESIGN AND METHODS: The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. RESULTS: Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6-23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0-4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β -7.0 g/day, 95% CI -12.4 to -1.7 per additional LP allele), nonalcoholic beverages (β -18.0 g/day, 95% CI -34.4 to -1.6), and wine (β -4.8 g/day, 95% CI -9.1 to -0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratioper 15 g/day 0.99, 95% CI 0.93-1.05). CONCLUSIONS: rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result.
OBJECTIVE: To estimate the causal association between intake of dairy products and incident type 2 diabetes. RESEARCH DESIGN AND METHODS: The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. RESULTS: Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6-23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0-4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β -7.0 g/day, 95% CI -12.4 to -1.7 per additional LP allele), nonalcoholic beverages (β -18.0 g/day, 95% CI -34.4 to -1.6), and wine (β -4.8 g/day, 95% CI -9.1 to -0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratioper 15 g/day 0.99, 95% CI 0.93-1.05). CONCLUSIONS: rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result.
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