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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #341869
Title: Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study

Author
item DING, MING - Harvard University
item HUANG, TAO - Harvard University
item BERGHOLDT, HELLE - University Of Copenhagen
item FRAZIER WOOD, ALEXIS - Baylor College Of Medicine
item ASLIBEKYAN, STELLA - University Of Alabama
item NORTH, KARI - University Of North Carolina
item VOORTMAN, TRUDY - University Medical Center Utrecht
item GRAFF, MARIAELISA - University Of North Carolina
item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Lai, Chao Qiang
item VARBO, ANETTE - University Of Copenhagen
item LEMAITRE, ROZENN - University Of Washington
item DE JONGE, ESTER - University Medical Center Utrecht
item FUMERON, FREDERIC - Centre De Recherche Sur Les Macromolécules Végétales (CERMAV)
item CORELLA, DOLORES - University Of Valencia
item WANG, CAROL - University Of Western Australia
item TJONNELAND, ANNE - Danish Cancer Society Research Center
item OVERVAD, KIM - Aarhus University
item SORENSEN, THORKILD - University Of Copenhagen
item FEITOSA, MARY - Washington University
item WOJCZYNSKI, MARY - Washington University
item KAHONEN, MIKA - University Of Tampere
item AHMAD, SHAFQAT - Lund University
item TRNDYTOM, FRIDA - Lund University
item PSATY, BRUCE - University Of Washington
item SISCOVICK, DAVID - New York Academy Of Medicine
item BARROSO, INES - Wellcome Trust Sanger Institute
item JOHANSSON, INGEGERD - University Of Umea
item HERNANDEZ, DENA - National Institutes Of Health (NIH)
item FERRUCCI, LUIGI - National Institutes Of Health (NIH)
item BANDINELLI, STEFANIA - Tuscany Regional Health Agency
item LINNEBERG, ALLAN - Research Centre For Prevention And Health
item SANDHOLT, CAMILLA - University Of Copenhagen
item PEDERSEN, OLUF - University Of Copenhagen
item HANSEN, TORBEN - University Of Copenhagen
item SCHULZ, CHRISTINA - Lund University
item SONESTEDT, EMILY - Lund University
item ORHO-MELANDER, MARJU - Lund University
item CHEN, TZU-AN - Baylor College Of Medicine
item ROTTER, JEROME - Los Angeles Biomedical Research Institute
item ALLISON, MATHEW - University Of California
item RICH, STEPHEN - University Of Virginia
item SORLI, JOSE - University Of Valencia
item COLTELL, OSCAR - University Jaume I Of Castellon
item PENNELL, CRAIG - University Of Western Australia
item EASTWOOD, PETER - University Of Western Australia
item HOFMAN, ALBERT - University Medical Center Utrecht
item UITTERLINDEN, ANDRE - University Medical Center Utrecht
item ZILLIKENS, M. CAROLA - University Medical Center Utrecht
item VAN ROOIJ, FRANK - University Medical Center Utrecht
item CHU, AUDREY - Harvard University
item ROSE, LYNDA - Harvard University
item RIDKER, PAUL - Harvard University
item VIIKARI, JORMA - University Of Turku
item RAITAKARA, OLLI - University Of Turku
item LEHTIMAKI, TERHO - University Of Tampere
item MIKKILA, VERA - University Of Helsinki
item WILLETT, WALTER - Harvard University
item WANG, YUJIE - University Of North Carolina
item TUCKER, KATHERINE - University Of Massachusetts
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item KILPELAINEN, TUOMAS - University Of Copenhagen
item PROVINCE, MICHAEL - Washington University
item FRANKS, PAUL - Lund University
item ARNETT, DONNA - University Of Alabama
item TANAKA, TOSHIKO - National Institutes Of Health (NIH)
item TOFT, ULLA - Research Centre For Prevention And Health
item ERICSON, ULRIKA - Lund University
item FRANCO, OSCAR - University Medical Center Utrecht
item MOZAFFARIAN, DARIUSH - Tufts University
item HU, FRANK - Harvard University
item CHASMAN, DANIEL - Harvard University
item NORDESTGAARD, BORGE - University Of Copenhagen
item ELLERVIK, CHRISTINA - Boston Children'S Hospital
item QI, LU - Harvard University

Submitted to: British Medical Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2017
Publication Date: 3/16/2017
Citation: Ding, M., Huang, T., Bergholdt, H.K., Frazier Wood, A.C., Aslibekyan, S., North, K.E., Voortman, T., Graff, M., Smith, C.E., Lai, C., Varbo, A., Lemaitre, R.N., De Jonge, E.A., Fumeron, F., Corella, D., Wang, C.A., Tjonneland, A., Overvad, K., Sorensen, T.I., Feitosa, M.F., Wojczynski, M.K., Kahonen, M., Ahmad, S., Trndytom, F., Psaty, B.M., Siscovick, D.S., Barroso, I., Johansson, I., Hernandez, D.G., Ferrucci, L., Bandinelli, S., Linneberg, A., Sandholt, C.H., Pedersen, O., Hansen, T., Schulz, C., Sonestedt, E., Orho-Melander, M., Chen, T., Rotter, J.I., Allison, M.A., Rich, S.S., Sorli, J.V., Coltell, O., Pennell, C.E., Eastwood, P., Hofman, A., Uitterlinden, A.G., Zillikens, M., Van Rooij, F.J., Chu, A.Y., Rose, L.M., Ridker, P.M., Viikari, J., Raitakara, O., Lehtimaki, T., Mikkila, V., Willett, W.C., Wang, Y., Tucker, K.L., Ordovas, J.M., Kilpelainen, T.O., Province, M.A., Franks, P.W., Arnett, D.K., Tanaka, T., Toft, U., Ericson, U., Franco, O.H., Mozaffarian, D., Hu, F.B., Chasman, D.I., Nordestgaard, B.G., Ellervik, C., Qi, L. 2017. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study. British Medical Journal. doi: 10.1136/bmj.j1000.

Interpretive Summary: Previous studies have reported that the intake of dairy foods lowers blood pressure and reduces hypertension. These studies relied on questionnaires to estimate dairy consumption, and the information collected through these methods may be imprecise. However, other methods of estimating dairy consumption may be more accurate. For example, dairy food estimates may be amenable to approaches that use genetics. One of these genetic approaches is called Mendelian randomization, and for dairy foods, Mendelian Randomization relies on a mutation in a single gene called lactase. The lactase mutation determines who is lactose-tolerant and can easily consume dairy foods. This allows us to use the presence of the mutation to represent dairy intake. The current study used Mendelian randomization to investigate relationships among the lactase gene mutation, the consumption of dairy foods, and blood pressure in over 197,000 people. This large-scale study began by combining results from 22 cross-sectional (one point in time) studies from around the world. In order to strengthen their results, the authors analyzed 10 additional "prospective studies" (carried out in 26,000 people) and 8 clinical trials. Prospective studies provide a higher level of evidence than cross-sectional studies because they look at changes in blood pressure over time. Clinical trials show the "before and after" effects of giving people dairy foods and are considered the highest level of evidence. Conclusions from these different types of studies were mixed. The lactase genetic mutations were associated with greater dairy intake, as the authors expected. However, the mutation was not associated with lower blood pressure or less hypertension. These findings may suggest that reliance on a single food group (like dairy foods) to address a complex disease (like hypertension) may not be the most effective approach. Instead we may need to study the overall dietary pattern and its connection to age-related diseases.

Technical Abstract: Objective: To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. Design: Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. Setting: CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. Participants: Data from 22 studies with 171,213 participants, and an additional 10 published prospective studies with 26,119 participants included in the observational analysis. Main Outcome Measures: The instrumental variable estimation was conducted using the ratio of coefficients approach. Using meta-analysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. Results: Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). Conclusion: The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.