Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study

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 KühnOlatz 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

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4 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)568-575
JournalDiabetes Care
Issue number4
Early online date20 Mar 2019
Publication statusEarly online date - 20 Mar 2019
Externally publishedYes

Bibliographical note

© 2019 by the American Diabetes Association.


  • Adult
  • Animals
  • Case-Control Studies
  • Cohort Studies
  • Dairy Products
  • Diabetes Mellitus, Type 2/epidemiology
  • Eating/physiology
  • Female
  • Gene-Environment Interaction
  • Genotype
  • Humans
  • Incidence
  • Lactase/genetics
  • Male
  • Mendelian Randomization Analysis
  • Middle Aged
  • Milk
  • Neoplasms/epidemiology
  • Nutrition Assessment
  • Polymorphism, Single Nucleotide
  • Risk Factors

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    Vissers, L. E. T., Sluijs, I., van der Schouw, Y. T., Forouhi, N. G., Imamura, F., Burgess, S., Barricarte, A., Boeing, H., Bonet, C., Chirlaque, M-D., Fagherazzi, G., Franks, P. W., Freisling, H., Gunter, M. J., Quirós, J. R., Ibsen, D. B., Kaaks, R., Key, T., Khaw, K. T., ... Wareham, N. J. (2019). Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study. Diabetes Care, 42(4), 568-575. https://doi.org/10.2337/dc18-2034