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

Ming Ding; Tao Huang; Helle K M Bergholdt; Thorkild I.A. Sørensen; Allan René Linneberg; Camilla Helene Sandholt; Oluf  Pedersen; Torben Hansen; Tuomas O Kilpeläinen; CHARGE Consortium; Børge G Nordestgaard; Christina Ellervik; Lu Qi; Mendelian Randomization of Dairy Consumption Working Group

doi:10.1136/bmj.j1000

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

Ming Ding, Tao Huang, Helle K M Bergholdt, Thorkild I.A. Sørensen, Allan René Linneberg, Camilla Helene Sandholt, Oluf Pedersen, Torben Hansen, Tuomas O Kilpeläinen, CHARGE Consortium, Børge G Nordestgaard, Christina Ellervik, Lu Qi, Mendelian Randomization of Dairy Consumption Working Group

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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 (β=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: β=-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.

Original language	English
Article number	j1000
Journal	The BMJ
Volume	356
Number of pages	10
ISSN	0959-8146
DOIs	https://doi.org/10.1136/bmj.j1000
Publication status	Published - 2017

Keywords

Blood Pressure
Dairy Products
Feeding Behavior
Genetic Predisposition to Disease
Humans
Hypertension
Lactase
Mendelian Randomization Analysis
Observational Studies as Topic
Polymorphism, Single Nucleotide
Randomized Controlled Trials as Topic
Journal Article
Meta-Analysis
Review

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Ding, M., Huang, T., Bergholdt, H. K. M., Sørensen, T. I. A., Linneberg, A. R., Sandholt, C. H., Pedersen, O., Hansen, T., Kilpeläinen, T. O., CHARGE Consortium, Nordestgaard, B. G., Ellervik, C., Qi, L., & Mendelian Randomization of Dairy Consumption Working Group (2017). Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study. The BMJ, 356, [j1000]. https://doi.org/10.1136/bmj.j1000

Ding, M, Huang, T, Bergholdt, HKM, Sørensen, TIA , Linneberg, AR, Sandholt, CH, Pedersen, O , Hansen, T , Kilpeläinen, TO, CHARGE Consortium, Nordestgaard, BG, Ellervik, C, Qi, L & Mendelian Randomization of Dairy Consumption Working Group 2017, 'Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study', The BMJ, vol. 356, j1000. https://doi.org/10.1136/bmj.j1000

@article{0e1f3519bb7c441a829e80f3eecba6fa,

title = "Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study",

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 (β=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: β=-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.",

keywords = "Blood Pressure, Dairy Products, Feeding Behavior, Genetic Predisposition to Disease, Humans, Hypertension, Lactase, Mendelian Randomization Analysis, Observational Studies as Topic, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Journal Article, Meta-Analysis, Review",

author = "Ming Ding and Tao Huang and Bergholdt, {Helle K M} and S{\o}rensen, {Thorkild I.A.} and Linneberg, {Allan Ren{\'e}} and Sandholt, {Camilla Helene} and Oluf Pedersen and Torben Hansen and Kilpel{\"a}inen, {Tuomas O} and {CHARGE Consortium} and Nordestgaard, {B{\o}rge G} and Christina Ellervik and Lu Qi and {Mendelian Randomization of Dairy Consumption Working Group}",

note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.",

year = "2017",

doi = "10.1136/bmj.j1000",

language = "English",

volume = "356",

journal = "The BMJ",

issn = "0959-8146",

publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Dairy consumption, systolic blood pressure, and risk of hypertension

T2 - Mendelian randomization study

AU - Ding, Ming

AU - Huang, Tao

AU - Bergholdt, Helle K M

AU - Sørensen, Thorkild I.A.

AU - Linneberg, Allan René

AU - Sandholt, Camilla Helene

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Kilpeläinen, Tuomas O

AU - CHARGE Consortium

AU - Nordestgaard, Børge G

AU - Ellervik, Christina

AU - Qi, Lu

AU - Mendelian Randomization of Dairy Consumption Working Group

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PY - 2017

Y1 - 2017

N2 - 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 (β=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: β=-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.

AB - 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 (β=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: β=-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.

KW - Blood Pressure

KW - Dairy Products

KW - Feeding Behavior

KW - Genetic Predisposition to Disease

KW - Humans

KW - Hypertension

KW - Lactase

KW - Mendelian Randomization Analysis

KW - Observational Studies as Topic

KW - Polymorphism, Single Nucleotide

KW - Randomized Controlled Trials as Topic

KW - Journal Article

KW - Meta-Analysis

KW - Review

UR - http://www.bmj.com/content/358/bmj.j3550

U2 - 10.1136/bmj.j1000

DO - 10.1136/bmj.j1000

M3 - Journal article

C2 - 28302601

SN - 0959-8146

VL - 356

JO - The BMJ

JF - The BMJ

M1 - j1000

ER -

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

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Keywords

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