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

Ming Ding, Tao Huang, Helle K. M. Bergholdt, Borge G. Nordestgaard, Christina Ellervik, Lu Qi, Alexis C. Frazier-Wood, Stella Aslibekyan, Kari E. North, Trudy Voortman, Mariaelisa Graff, Caren E. Smith, Chao-Qiang Lai, Anette Varbo, Rozenn N. Lemaitre, Ester A. L. de Jonge, Frederic Fumeron, Dolores Corella, Carol A. Wang, Anne Tjonneland & 56 others Kim Overvad, Thorkild I. A. Sorensen, Mary F. Feitosa, Mary K. Wojczynski, Mika Kahonen, Shafqat Ahmad, Frida Renstrom, Bruce M. Psaty, David S. Siscovick, Ines Barroso, Ingegerd Johansson, Dena Hernandez, Luigi Ferrucci, Stefania Bandinelli, Allan Linneberg, Camilla Helene Sandholt, Oluf Pedersen, Torben Hansen, Christina-Alexandra Schulz, Emily Sonestedt, Marju Orho-Melander, Tzu-An Chen, Jerome I. Rotter, Mathew A. Allison, Stephen S. Rich, Jose V. Sorli, Oscar Coltell, Craig E. Pennell, Peter R. Eastwood, Albert Hofman, Andre G. Uitterlinden, MCarola Zillikens, Frank J. A. van Rooij, Audrey Y. Chu, Lynda M. Rose, Paul M. Ridker, Jorma Viikari, Olli Raitakari, Terho Lehtimaki, Vera Mikkila, Walter C. Willett, Yujie Wang, Katherine L. Tucker, Jose M. Ordovas, Tuomas O. Kilpelainen, Michael A. Province, Paul W. Franks, Donna K. Arnett, Toshiko Tanaka, Ulla Toft, Ulrika Ericso, Oscar H. Franco, Dariush Mozaffarian, Frank B. Hu, Daniel I. Chasman, CHARGE consortium

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 metaanalysis, 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

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 languageEnglish
Article number1000
Number of pages10
JournalBritish Medical Journal Open Access (Online )
Volume356
DOIs
Publication statusPublished - 16 Mar 2017

Cite this

Ding, M., Huang, T., Bergholdt, H. K. M., Nordestgaard, B. G., Ellervik, C., Qi, L., ... CHARGE consortium (2017). Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study. British Medical Journal Open Access (Online ), 356, [1000]. https://doi.org/10.1136/bmj.j1000
Ding, Ming ; Huang, Tao ; Bergholdt, Helle K. M. ; Nordestgaard, Borge G. ; Ellervik, Christina ; Qi, Lu ; Frazier-Wood, Alexis C. ; Aslibekyan, Stella ; North, Kari E. ; Voortman, Trudy ; Graff, Mariaelisa ; Smith, Caren E. ; Lai, Chao-Qiang ; Varbo, Anette ; Lemaitre, Rozenn N. ; de Jonge, Ester A. L. ; Fumeron, Frederic ; Corella, Dolores ; Wang, Carol A. ; Tjonneland, Anne ; Overvad, Kim ; Sorensen, Thorkild I. A. ; Feitosa, Mary F. ; Wojczynski, Mary K. ; Kahonen, Mika ; Ahmad, Shafqat ; Renstrom, Frida ; Psaty, Bruce M. ; Siscovick, David S. ; Barroso, Ines ; Johansson, Ingegerd ; Hernandez, Dena ; Ferrucci, Luigi ; Bandinelli, Stefania ; Linneberg, Allan ; Sandholt, Camilla Helene ; Pedersen, Oluf ; Hansen, Torben ; Schulz, Christina-Alexandra ; Sonestedt, Emily ; Orho-Melander, Marju ; Chen, Tzu-An ; Rotter, Jerome I. ; Allison, Mathew A. ; Rich, Stephen S. ; Sorli, Jose V. ; Coltell, Oscar ; Pennell, Craig E. ; Eastwood, Peter R. ; Hofman, Albert ; Uitterlinden, Andre G. ; Zillikens, MCarola ; van Rooij, Frank J. A. ; Chu, Audrey Y. ; Rose, Lynda M. ; Ridker, Paul M. ; Viikari, Jorma ; Raitakari, Olli ; Lehtimaki, Terho ; Mikkila, Vera ; Willett, Walter C. ; Wang, Yujie ; Tucker, Katherine L. ; Ordovas, Jose M. ; Kilpelainen, Tuomas O. ; Province, Michael A. ; Franks, Paul W. ; Arnett, Donna K. ; Tanaka, Toshiko ; Toft, Ulla ; Ericso, Ulrika ; Franco, Oscar H. ; Mozaffarian, Dariush ; Hu, Frank B. ; Chasman, Daniel I. ; CHARGE consortium. / Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study. In: British Medical Journal Open Access (Online ). 2017 ; Vol. 356.
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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.DESIGNMendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable.SETTINGCHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.PARTICIPANTSData 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 MEASURESThe instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized.RESULTSCompared 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; PCONCLUSIONThe 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 = "DOSE-RESPONSE METAANALYSIS, CONTROLLED-TRIALS, CARDIOVASCULAR-DISEASE, INCIDENT HYPERTENSION, METABOLIC SYNDROME, GENETIC-VARIANTS, BODY-WEIGHT, MILK, ADULTS, FAT",
author = "Ming Ding and Tao Huang and Bergholdt, {Helle K. M.} and Nordestgaard, {Borge G.} and Christina Ellervik and Lu Qi and Frazier-Wood, {Alexis C.} and Stella Aslibekyan and North, {Kari E.} and Trudy Voortman and Mariaelisa Graff and Smith, {Caren E.} and Chao-Qiang Lai and Anette Varbo and Lemaitre, {Rozenn N.} and {de Jonge}, {Ester A. L.} and Frederic Fumeron and Dolores Corella and Wang, {Carol A.} and Anne Tjonneland and Kim Overvad and Sorensen, {Thorkild I. A.} and Feitosa, {Mary F.} and Wojczynski, {Mary K.} and Mika Kahonen and Shafqat Ahmad and Frida Renstrom and Psaty, {Bruce M.} and Siscovick, {David S.} and Ines Barroso and Ingegerd Johansson and Dena Hernandez and Luigi Ferrucci and Stefania Bandinelli and Allan Linneberg and Sandholt, {Camilla Helene} and Oluf Pedersen and Torben Hansen and Christina-Alexandra Schulz and Emily Sonestedt and Marju Orho-Melander and Tzu-An Chen and Rotter, {Jerome I.} and Allison, {Mathew A.} and Rich, {Stephen S.} and Sorli, {Jose V.} and Oscar Coltell and Pennell, {Craig E.} and Eastwood, {Peter R.} and Albert Hofman and Uitterlinden, {Andre G.} and MCarola Zillikens and {van Rooij}, {Frank J. A.} and Chu, {Audrey Y.} and Rose, {Lynda M.} and Ridker, {Paul M.} and Jorma Viikari and Olli Raitakari and Terho Lehtimaki and Vera Mikkila and Willett, {Walter C.} and Yujie Wang and Tucker, {Katherine L.} and Ordovas, {Jose M.} and Kilpelainen, {Tuomas O.} and Province, {Michael A.} and Franks, {Paul W.} and Arnett, {Donna K.} and Toshiko Tanaka and Ulla Toft and Ulrika Ericso and Franco, {Oscar H.} and Dariush Mozaffarian and Hu, {Frank B.} and Chasman, {Daniel I.} and {CHARGE consortium}",
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Ding, M, Huang, T, Bergholdt, HKM, Nordestgaard, BG, Ellervik, C, Qi, L, Frazier-Wood, AC, Aslibekyan, S, North, KE, Voortman, T, Graff, M, Smith, CE, Lai, C-Q, Varbo, A, Lemaitre, RN, de Jonge, EAL, Fumeron, F, Corella, D, Wang, CA, Tjonneland, A, Overvad, K, Sorensen, TIA, Feitosa, MF, Wojczynski, MK, Kahonen, M, Ahmad, S, Renstrom, F, Psaty, BM, Siscovick, DS, Barroso, I, Johansson, I, Hernandez, D, Ferrucci, L, Bandinelli, S, Linneberg, A, Sandholt, CH, Pedersen, O, Hansen, T, Schulz, C-A, Sonestedt, E, Orho-Melander, M, Chen, T-A, Rotter, JI, Allison, MA, Rich, SS, Sorli, JV, Coltell, O, Pennell, CE, Eastwood, PR, Hofman, A, Uitterlinden, AG, Zillikens, MC, van Rooij, FJA, Chu, AY, Rose, LM, Ridker, PM, Viikari, J, Raitakari, O, Lehtimaki, T, Mikkila, V, Willett, WC, Wang, Y, Tucker, KL, Ordovas, JM, Kilpelainen, TO, Province, MA, Franks, PW, Arnett, DK, Tanaka, T, Toft, U, Ericso, U, Franco, OH, Mozaffarian, D, Hu, FB, Chasman, DI & CHARGE consortium 2017, 'Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study' British Medical Journal Open Access (Online ), vol. 356, 1000. https://doi.org/10.1136/bmj.j1000

Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study. / Ding, Ming; Huang, Tao; Bergholdt, Helle K. M.; Nordestgaard, Borge G.; Ellervik, Christina; Qi, Lu; Frazier-Wood, Alexis C.; Aslibekyan, Stella; North, Kari E.; Voortman, Trudy; Graff, Mariaelisa; Smith, Caren E.; Lai, Chao-Qiang; Varbo, Anette; Lemaitre, Rozenn N.; de Jonge, Ester A. L.; Fumeron, Frederic; Corella, Dolores; Wang, Carol A.; Tjonneland, Anne; Overvad, Kim; Sorensen, Thorkild I. A.; Feitosa, Mary F.; Wojczynski, Mary K.; Kahonen, Mika; Ahmad, Shafqat; Renstrom, Frida; Psaty, Bruce M.; Siscovick, David S.; Barroso, Ines; Johansson, Ingegerd; Hernandez, Dena; Ferrucci, Luigi; Bandinelli, Stefania; Linneberg, Allan; Sandholt, Camilla Helene; Pedersen, Oluf; Hansen, Torben; Schulz, Christina-Alexandra; Sonestedt, Emily; Orho-Melander, Marju; Chen, Tzu-An; Rotter, Jerome I.; Allison, Mathew A.; Rich, Stephen S.; Sorli, Jose V.; Coltell, Oscar; Pennell, Craig E.; Eastwood, Peter R.; Hofman, Albert; Uitterlinden, Andre G.; Zillikens, MCarola; van Rooij, Frank J. A.; Chu, Audrey Y.; Rose, Lynda M.; Ridker, Paul M.; Viikari, Jorma; Raitakari, Olli; Lehtimaki, Terho; Mikkila, Vera; Willett, Walter C.; Wang, Yujie; Tucker, Katherine L.; Ordovas, Jose M.; Kilpelainen, Tuomas O.; Province, Michael A.; Franks, Paul W.; Arnett, Donna K.; Tanaka, Toshiko; Toft, Ulla; Ericso, Ulrika; Franco, Oscar H.; Mozaffarian, Dariush; Hu, Frank B.; Chasman, Daniel I.; CHARGE consortium.

In: British Medical Journal Open Access (Online ), Vol. 356, 1000, 16.03.2017.

Research output: Contribution to journalArticle

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 - Nordestgaard, Borge G.

AU - Ellervik, Christina

AU - Qi, Lu

AU - Frazier-Wood, Alexis C.

AU - Aslibekyan, Stella

AU - North, Kari E.

AU - Voortman, Trudy

AU - Graff, Mariaelisa

AU - Smith, Caren E.

AU - Lai, Chao-Qiang

AU - Varbo, Anette

AU - Lemaitre, Rozenn N.

AU - de Jonge, Ester A. L.

AU - Fumeron, Frederic

AU - Corella, Dolores

AU - Wang, Carol A.

AU - Tjonneland, Anne

AU - Overvad, Kim

AU - Sorensen, Thorkild I. A.

AU - Feitosa, Mary F.

AU - Wojczynski, Mary K.

AU - Kahonen, Mika

AU - Ahmad, Shafqat

AU - Renstrom, Frida

AU - Psaty, Bruce M.

AU - Siscovick, David S.

AU - Barroso, Ines

AU - Johansson, Ingegerd

AU - Hernandez, Dena

AU - Ferrucci, Luigi

AU - Bandinelli, Stefania

AU - Linneberg, Allan

AU - Sandholt, Camilla Helene

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Schulz, Christina-Alexandra

AU - Sonestedt, Emily

AU - Orho-Melander, Marju

AU - Chen, Tzu-An

AU - Rotter, Jerome I.

AU - Allison, Mathew A.

AU - Rich, Stephen S.

AU - Sorli, Jose V.

AU - Coltell, Oscar

AU - Pennell, Craig E.

AU - Eastwood, Peter R.

AU - Hofman, Albert

AU - Uitterlinden, Andre G.

AU - Zillikens, MCarola

AU - van Rooij, Frank J. A.

AU - Chu, Audrey Y.

AU - Rose, Lynda M.

AU - Ridker, Paul M.

AU - Viikari, Jorma

AU - Raitakari, Olli

AU - Lehtimaki, Terho

AU - Mikkila, Vera

AU - Willett, Walter C.

AU - Wang, Yujie

AU - Tucker, Katherine L.

AU - Ordovas, Jose M.

AU - Kilpelainen, Tuomas O.

AU - Province, Michael A.

AU - Franks, Paul W.

AU - Arnett, Donna K.

AU - Tanaka, Toshiko

AU - Toft, Ulla

AU - Ericso, Ulrika

AU - Franco, Oscar H.

AU - Mozaffarian, Dariush

AU - Hu, Frank B.

AU - Chasman, Daniel I.

AU - CHARGE consortium

PY - 2017/3/16

Y1 - 2017/3/16

N2 - OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal.DESIGNMendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable.SETTINGCHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.PARTICIPANTSData 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 MEASURESThe instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized.RESULTSCompared 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; PCONCLUSIONThe 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.DESIGNMendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable.SETTINGCHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.PARTICIPANTSData 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 MEASURESThe instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized.RESULTSCompared 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; PCONCLUSIONThe 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 - DOSE-RESPONSE METAANALYSIS

KW - CONTROLLED-TRIALS

KW - CARDIOVASCULAR-DISEASE

KW - INCIDENT HYPERTENSION

KW - METABOLIC SYNDROME

KW - GENETIC-VARIANTS

KW - BODY-WEIGHT

KW - MILK

KW - ADULTS

KW - FAT

U2 - 10.1136/bmj.j1000

DO - 10.1136/bmj.j1000

M3 - Article

VL - 356

JO - BMJ: British Medical Journal

JF - BMJ: British Medical Journal

SN - 0959-535X

M1 - 1000

ER -