Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study
Year: 2019
Type: article
Study design: Observational Study
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.
Source: Diabetes Care
DOI: 10.2337/dc18-2034
Authors: Linda E.T. Vissers, Ivonne Sluijs, Yvonne T. van der Schouw, Nita G. Forouhi, Fumiaki Imamura, Stephen Burgess, Aurelio Barricarte, Heiner Boeing, Catalina Bonet, Maria-Dolores Chirlaque, Guy Fagherazzi, Paul W. Franks, Heinz Freisling, Marc J. Gunter, J. Ramón Quirós, Daniel B. Ibsen, Rudolf Kaaks, Timothy Key, Kay T. Khaw, Tilman Kühn, Olatz Mokoroa, Peter M. Nilsson, Kim Overvad, Valeria Pala, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Annemieke M.W. Spijkerman, Anne Tjonneland, Rosario Tumino, Miguel Rodríguez-Barranco, Olov Rolandsson, Elio Riboli, Stephen J. Sharp, Claudia Langenberg, Nicholas J. Wareham
Institutions: Utrecht University, University Medical Center Utrecht, University of Cambridge, MRC Epidemiology Unit, German Institute of Human Nutrition, Institut Català d'Oncologia, Instituto Murciano de Investigación Biosanitaria, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Universidad de Murcia, Inserm, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, Lund University, Centre international de recherche sur le cancer, Gobierno del Principado de Asturias, Aarhus University, German Cancer Research Center, University of Oxford, Biogipuzkoa Health Research Institute, Aalborg University Hospital, Fondazione IRCCS Istituto Nazionale dei Tumori, Federico II University Hospital, University of Naples Federico II, Piedmont Reference Center for Epidemiology and Cancer Prevention, University of Turin, National Institute for Public Health and the Environment, Danish Cancer Society, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Andalusian School of Public Health, Umeå University, Imperial College London
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: World Health Organization, Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, European Commission, Cambridge University Hospitals, Universitair Medisch Centrum Utrecht, Novo Nordisk, Vetenskapsrådet, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Sixth Framework Programme, Medical Research Council, World Cancer Research Fund, Agentschap NL, NIHR Cambridge Biomedical Research Centre
Awards: Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, G1075599542, Aetiology of type 2 diabetes and related metabolic disorders, Nutritional epidemiology, G139696651, NIHR Senior Investigator Award, G2341417990, Large-scale integrative genomic studies of high-dimensional traits in cardiovascular diseases (renewal), G2826529823, G2892497062, G299057155, G370598735, G469522804, G4990591557, G515689015, G5787426001, G5897142711, G6085534252, NIHR Senior Investigator Award, G6206044308, G6594529311, G6641991021, G6957823285, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application (renewal). (Joint funding with MRC), Livestock, Environment and People (LEAP), NIHR Senior Investigator Award, G8585681489, NIHR Senior Investigator Award, G892496435, G8944598329, G899966268
OpenAlex ID: W2912846750