Journal
BMJ-BRITISH MEDICAL JOURNAL
Volume 356, Issue -, Pages -Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/bmj.j1000
Keywords
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Categories
Funding
- National Heart, Lung, and Blood Institute [HL071981, HL034594, HL126024, HL043851, HL080467, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK091718, DK100383, DK078616]
- Boston Obesity Nutrition Research Center [DK46200]
- United States-Israel Binational Science Foundation [2011036]
- American Heart Association Scientist Development Award [0730094N]
- Danish Council for Independent Research
- Medical Sciences (FSS)
- Herlev Hospital
- Copenhagen University Hospital
- Copenhagen County Foundation
- Chief Physician Johan Boserup and Lise Boserup's Fund, Denmark
- Region Zealand Foundation
- Naestved Hospital Foundation
- Edith and Henrik Henriksens Memorial Scholarship
- Johan and Lise Boserup Foundation
- TrygFonden
- Johannes Fog's Foundation, Region Zealand
- Naestved Hospital
- National Board of Health
- Local Government Denmark Foundation
- National Cancer Institute [CA047988]
- Donald W Reynolds Foundation
- Fondation Leducq
- Amgen
- National Institutes of Health [UM1 CA186107, P01 CA87969, R01 CA49449, R01 HL034594, R01 HL088521, UM1 CA167552, R01 HL35464, HL073168, CA87969, CA49449]
- Merck Research Laboratories, North Wales, PA
- Arthur Ashley Williams Foundation
- Harvard ophthalmology scholar award (Harvard Medical School) from the Harvard Glaucoma Center of Excellence
- National Human Genome Research Institute [U01HG004402]
- NIH roadmap for medical research
- Danish Research Councils
- Health Foundation
- Danish Centre for Evaluation and Health Technology Assessment
- Copenhagen County
- Danish Heart Foundation
- Ministry of Health and Prevention
- Association of Danish Pharmacies
- Augustinus Foundation
- Novo Nordisk
- Velux Foundation
- Becket Foundation
- Ib Henriksens Foundation
- INSERM
- CNAMTS
- Lilly
- Novartis Pharma
- Sanofi-Aventis
- INSERM (Reseaux en Sante Publique, Interactions entre les determinants de la sante, Cohortes Sante TGIR)
- Association Diabete Risque Vasculaire
- Federation Francaise de Cardiologie
- La Fondation de France
- ALFEDIAM
- CNIEL
- ONIVINS
- Societe Francophone du Diabete
- Ardix Medical
- Bayer Diagnostics
- Becton Dickinson
- Cardionics
- Merck Sante
- Pierre Fabre
- Roche
- Topcon
- Erasmus Medical Center
- Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- Netherlands Organisation of Scientific Research NWO [175.010.2005.011, 911-03-012]
- Research Institute for Diseases in the Elderly (014-93-015
- RIDE2), the Netherlands Genomics Initiative (NGI)/ Netherlands Organisation for Scientific Research (NWO) [050-060-810]
- Region Skane
- City of Malmo
- Pahlsson Foundation
- Swedish Heart and Lung Foundation
- Swedish Heart-Lung Foundation
- Swedish Diabetes Association
- Pahlsson's Foundation
- Swedish Research Council
- Umea Medical Research Foundation
- Heart Foundation of Northern Sweden
- Wellcome Trust [WT098051]
- NCRR [UL1-TR-000040, UL1-TR-001079]
- NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295]
- National Institute of Neurological Disorders and Stroke (NINDS)
- National Institute on Aging (NIA) [R01AG023629]
- National Center for Advancing Translational Sciences, CTSI grant [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant [DK063491]
- Academy of Finland [286284, 134309, 126925, 121584, 124282, 129378, 117787, 41071]
- Social Insurance Institution of Finland
- Kuopio University Hospital Medical Fund [X51001]
- Tampere University Hospital Medical Fund [X51001]
- Turku University Hospital Medical Fund [X51001]
- Juho Vainio Foundation
- Paavo Nurmi Foundation
- Finnish Foundation of Cardiovascular Research
- Finnish Cultural Foundation
- Tampere Tuberculosis Foundation
- Emil Aaltonen Foundation
- Yrjo Jahnsson Foundation
- Danish Ministry of Science, Technology and Innovation
- Danish Council for Independent Research [DFF-333-00124, DFF-1331-00730B]
- Spanish Ministry of Health (Instituto de Salud Carlos III)
- Ministerio de Economia y Competitividad [G03/140, CIBER 06/03, RD06/0045 PI07-0954, CNIC-06, PI11/02505, SAF2009-12304, AGL2010-22319-C03-03, PRX14/00527]
- Fondo Europeo de Desarrollo Regional
- University Jaume I [P1-1B2013-54]
- Generalitat Valenciana [AP111/10, AP-042/11, BEST/2015/087, GVACOMP2011-151, ACOMP/2011/145, ACOMP/2012/190, ACOMP/2013/159]
- National Heart, Lung, and Blood Institute (NHLBI) [U01HL072524, R01 HL091357, HL54776, HL078885]
- US Department of Agriculture, Agriculture Research Service [53-K06-5-10, 58-1950-9-001]
- National Health and Medical Research Council of Australia [403981, 003209]
- Canadian Institutes of Health Research [MOP-82893]
- NHMRC [1027449, 1044840, 1021855]
- Safework Australia
- Italian Ministry of Health [ICS110.1/RF97.71]
- US National Institute on Aging [263 MD 9164, 263 MD 821336]
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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<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.
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