title: Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study.
abstract: ObjectiveTo 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 meta-analysis, 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) ofLCT-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). UsingLCT-13910rs4988235 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).ConclusionThe 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.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.|Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark.|Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg Frederiksberg, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Helle Km
authors.initials: HK
authors.lastname: Bergholdt
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.|Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Production, Research and Innovation, Region Sjælland, Sorø, Denmark.|Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Ellervik
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA lqi1@tulane.edu.|Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D001794:Blood Pressure / Q000235:genetics; D003611:Dairy Products; D005247:Feeding Behavior / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D043322:Lactase / Q000235:genetics*; D057182:Mendelian Randomization Analysis; D064887:Observational Studies as Topic; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic
chemical_list: D043322:Lactase