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Research Project: Childhood Obesity Prevention

Location: Children's Nutrition Research Center

Title: Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study

item DING, MING - Harvard School Of Public Health
item HUANG, TAO - Harvard School Of Public Health
item FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item ASLIBEKYAN, STELLA - University Of Alabama
item NORTH, KARI - University Of North Carolina
item VOORTMAN, TRUDY - Erasmus Medical Center
item GRAFF, MARIAELISA - University Of North Carolina
item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LAO, CHAO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item VARBO, ANETTE - University Of Copenhagen

Submitted to: British Medical Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2017
Publication Date: 3/16/2017
Citation: Ding, M., Huang, T., Frazier-Wood, A.C., Aslibekyan, S., North, K.E., Voortman, T., Graff, M., Smith, C.E., Lao, C.Q., Varbo, A., Lematire, R. N., de Jonge, E.A., Fumeron, F., Corella, D., Wang, C.A., Tjonneland, A., Overad, K., Sorensen T.I., Feitosa, M.F., Wojczynski, M.K., Kahonen, M., Ahmad, S., Renstrom, F., Psaty, B.M., Siscovick, D.S., Barroso, I., Johansson, I., Hernandez, D., Ferrucci, L, Bandinelli, S., Linneberg, A., Sandholt, C.H., Pedersen, O., Hansen, T., Schulz, C.A., Sonestedt, E., Orho-Melander, M., Chen, T.A., Rotter, J.I., Allison, M.A., Rich, S.S., Sorli, J.V., Coltell, O., Pennell, C.E., Eastwood, P.R., Hofman, A., Uitterlinden, A.G., Zillikens, M.C., van Rooij, F.J., Chu, A.Y., Rose, L.M., Ridker, P.M., Viikari, J., Raitakari, O., Lehtimaki, T., Mikkila, V., Willett, W.C., Wang, Y., Tucker, K.L., Ordovas, J.M., Kilpelainen,m T.O., Province, M.A., Franks, P.W., Arnett, D.K., Tanaka, T., Toft, U., Ericson, U., Franco, O.H., CHARGE consortium, Mozaffarian, D., Hu, F.B., Chasman, D.I., Nordestgaard, B.G., Ellevik, C., Qi, L. 2017. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study. British Medical Journal. 356:j1000.

Interpretive Summary: Eating dairy intake is thought to be associated with lower blood pressure. The problem is that it is not clear whether the dairy itself causes a lower blood pressure, or whether people who eat a lot of dairy also happen have a generally healthy lifestyle and it is the overall lifestyle which leads to an association to be seen between diary and lower blood pressure. This makes is hard to know whether individuals seeking to maintain a heathy blood pressure, or who are at a high risk of hypertension, should make efforts to consume dairy or not. To try to address this we analyzed data from over 180,000 adults across 25 studies, and looked whether dairy intake predicted blood pressure over time. We also performed a new type of analyses called "Mendelian randomization" which incorporates genetic information and helps better understand whether an environmental variable (such as dairy intake) is causally associated with a health outcome (such as blood pressure). Our analyses confirmed that higher dairy intake was associated with lower blood pressure but our Mendelian randomization analyses suggested that this association was not causal. This information will be helpful for developing dietary guidelines for the prevention of hypertension, and for healthcare practitioners who need to give guidelines for how to maintain a health blood pressure to patients.

Technical Abstract: This study examined whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. A Mendelian randomization study was employed, using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. Data from 22 studies with 171,213 participants, and an additional 10 published prospective studies with 26,119 participants included in the observational analysis. 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. 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 (B=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: B=-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). 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.