Evidence map›Paper›PMID 24974252›Full record

SynthesisThe lancet. Diabetes & endocrinology2014

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.

Karani S Vimaleswaran, Alana Cavadino, Diane J Berry, LifeLines Cohort Study investigators, Rolf Jorde, Aida Karina Dieffenbach, Chen Lu, Alexessander Couto Alves, Hiddo J Lambers Heerspink, Emmi Tikkanen and 98 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The lancet. Diabetes & endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers, 21 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
199citing papers in PubMed, 21 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

199 citing papers in PubMed, 21 syntheses or guidelines pooled it.

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  10. Association Between Vitamin D and Uric Acid in Adults: A Systematic Review and Meta-Analysis.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2020
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139 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

108 authors.

Karani S VimaleswaranPopulation, Policy and Practice, UCL Institute of Child Health, London, UK; Hugh Sinclair Unit of Human Nutrition, Department of Food & Nutritional Sciences, School of Chemistry, Food & Pharmacy, University of Reading, Reading, UK.
Alana CavadinoPopulation, Policy and Practice, UCL Institute of Child Health, London, UK.
Diane J BerryPopulation, Policy and Practice, UCL Institute of Child Health, London, UK.
LifeLines Cohort Study investigators
Rolf JordeTromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
Aida Karina DieffenbachDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Chen LuDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Alexessander Couto AlvesDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK; Institute of Health Sciences, University of Oulu, Oulu, Finland.
Hiddo J Lambers HeerspinkDepartment of Clinical Pharmacology, University Medical Center, University of Groningen, Groningen, Netherlands.
Emmi TikkanenInstitute for Molecular Medicine Finland, Tukholmankatu, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Hjelt Institute, University of Helsinki, Helsinki, Finland.
Joel ErikssonCentre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
Andrew WongMRC Unit for Lifelong Health and Ageing, University College London, London, UK.
Massimo ManginoDepartment of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Campus, London, UK.
Kathleen A JablonskiBiostatistics Center, Department of Epidemiology and Biostatistics, School of Public Health, George Washington University, Rockville, MD, USA.
Ilja M NolteDepartment of Epidemiology, University Medical Center, University of Groningen, Groningen, Netherlands.
Denise K HoustonGerontology and Geriatric Medicine, Department of Internal Medicine, and J Paul Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Tarunveer Singh AhluwaliaMetabolic Genetics, Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Pediatric Asthma Center, Gentofte Hospital, Copenhagen, Denmark.
Peter J van der MostDepartment of Epidemiology, University Medical Center, University of Groningen, Groningen, Netherlands.
Dorota PaskoGenetics of Complex Traits, University of Exeter Medical School, Exeter, UK.
Lina ZgagaCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK; Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
Elisabeth ThieringInstitute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Division of Metabolic Diseases and Nutritional Medicine, Ludwig Maximilian University of Munich, Dr von Hauner Children's Hospital, Munich, Germany.
Veronique VitartMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Ross M FraserCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Jennifer E HuffmanMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Rudolf A de BoerDepartment of Cardiology, University Medical Center, University of Groningen, Groningen, Netherlands.
Ben SchöttkerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Kai-Uwe SaumDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Mark I McCarthyOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, Oxford, UK.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
Karl-Heinz HerzigInstitute of Biomedicine, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland.
Sylvain SebertBiocenter Oulu, University of Oulu, Oulu, Finland; Institute of Health Sciences, University of Oulu, Oulu, Finland.
Anneli PoutaObstetrics and Gynecology, Department of Clinical Sciences, Oulu University Hospital, Oulu, Finland; National Institute for Health and Welfare, Oulu, Finland.
Jaana LaitinenFinnish Institute of Occupational Health, Helsinki, Finland.
Marcus E KleberMedical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Gerjan NavisDepartment of Internal Medicine, Division of Nephrology, University Medical Center, University of Groningen, Groningen, Netherlands.
Mattias LorentzonCentre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
Karen JamesonMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Nigel ArdenNIHR Oxford Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Jackie A CooperCardiovascular Genetics, BHF Laboratories, Institute of Cardiovascular Science, University College London, London, UK.
Jayshree AcharyaCardiovascular Genetics, BHF Laboratories, Institute of Cardiovascular Science, University College London, London, UK.
Rebecca HardyMRC Unit for Lifelong Health and Ageing, University College London, London, UK.
Olli RaitakariResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Samuli RipattiInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Liana K BillingsCenter for Human Genetic Research and Diabetes Research Center, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; NorthShore University HealthSystem, Evanston, IL, USA.
Jari LahtiInstitute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Clive OsmondMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Brenda W PenninxDepartment of Psychiatry, EMGO Institute, VU University Medical Centre, Amsterdam, Netherlands.
Lars RejnmarkDepartment of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Kurt K LohmanDepartment of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Lavinia PaternosterMRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Ronald P StolkDepartment of Epidemiology, University Medical Center, University of Groningen, Groningen, Netherlands.
Dena G HernandezLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Liisa BybergDepartment of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Emil HagströmUppsala Clinical Research Centre, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Håkan MelhusUppsala Clinical Research Centre, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Erik IngelssonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Uppsala Clinical Research Centre, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Dan MellströmCentre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
Osten LjunggrenUppsala Clinical Research Centre, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Ioanna TzoulakiFaculty of Medicine, School of Public Health, Imperial College London, London, UK.
Stela McLachlanCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Evropi TheodoratouCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Carla M T TieslerInstitute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilian University of Munich, Dr von Hauner Children's Hospital, Munich, Germany.
Antti JulaDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland.
Pau NavarroMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Alan F WrightMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Ozren PolasekCroatian Centre for Global Health, University of Split Medical School, Split, Croatia.
International Consortium for Blood Pressure (ICBP)
Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium
Global Blood Pressure Genetics (Global BPGen) consortium
Caroline Hayward
James F WilsonCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Igor RudanCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Veikko SalomaaNational Institute for Health and Welfare, Helsinki, Finland.
Joachim HeinrichInstitute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Harry CampbellCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Jacqueline F PriceCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Magnus KarlssonClinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Orthopaedic Surgery, Lund University, Skåne University Hospital, Malmö, Sweden.
Lars LindUppsala Clinical Research Centre, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Karl MichaëlssonDepartment of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Stefania BandinelliGeriatric Unit, Azienda Sanitaria Firenze, Florence, Italy.
Timothy M FraylingGenetics of Complex Traits, University of Exeter Medical School, Exeter, UK.
Catharina A HartmanDepartment of Psychiatry, University Medical Center, University of Groningen, Groningen, Netherlands.
Thorkild I A SørensenMetabolic Genetics, Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Stephen B KritchevskyGerontology and Geriatric Medicine, Department of Internal Medicine, and J Paul Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Bente Lomholt LangdahlDepartment of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Johan G ErikssonDepartment of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; Vasa Central Hospital, Vasa, Finland; Folkhälsan Research Centre, Helsinki, Finland; Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
Jose C FlorezCenter for Human Genetic Research and Diabetes Research Center, Massachusetts General Hospital, Boston, MA, USA.
Tim D SpectorDepartment of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Campus, London, UK.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
Diana KuhMRC Unit for Lifelong Health and Ageing, University College London, London, UK.
Steve E HumphriesCardiovascular Genetics, BHF Laboratories, Institute of Cardiovascular Science, University College London, London, UK.
Cyrus CooperNIHR Oxford Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Claes OhlssonCentre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
Winfried MärzMedical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Synlab Academy, Mannheim, Germany; Department of Internal Medicine, Division of Endocrinology and Metabolism, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Martin H de BorstDepartment of Internal Medicine, Division of Nephrology, University Medical Center, University of Groningen, Groningen, Netherlands.
Meena KumariDepartment of Epidemiology and Public Health, University College London, London, UK.
Mika KivimakiDepartment of Epidemiology and Public Health, University College London, London, UK.
Thomas J WangDivision of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
Chris PowerPopulation, Policy and Practice, UCL Institute of Child Health, London, UK.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Guri GrimnesTromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
Pim van der HarstDepartment of Cardiology, University Medical Center, University of Groningen, Groningen, Netherlands.
Harold SniederDepartment of Epidemiology, University Medical Center, University of Groningen, Groningen, Netherlands.
Aroon D HingoraniGenetic Epidemiology Group, University College London, London, UK.
Stefan PilzDepartment of Internal Medicine, Division of Endocrinology and Metabolism, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
John C WhittakerQuantitative Sciences, GlaxoSmithKline, Stevenage, UK.
Marjo-Riitta JärvelinDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK; MRC-PHE Centre for Environment & Health, Imperial College London, London, UK; Biocenter Oulu, University of Oulu, Oulu, Finland; Institute of Health Sciences, University of Oulu, Oulu, Finland; Unit of Primary Care, Oulu University Hospital, Oulu, Finland; National Institute for Health and Welfare, Oulu, Finland.
Elina HyppönenPopulation, Policy and Practice, UCL Institute of Child Health, London, UK; School of Population Health, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia. Electronic address: elina.hypponen@unisa.edu.au.

Funding

Multiethnic Study of Type 2 Diabetes GenesU01DK085526 · NIDDK · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, JABLONSKI, KATHLEEN ANN · 2009 to 2014
$15.7M
Fine-mapping and Characterization of Metabolic Loci in the DPP Outcomes StudyR01DK072041 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI FLOREZ, JOSE CARLOS · 2005 to 2017
$7.6M
British Heart Foundation PG/09/023British Heart Foundation PG/09/023/26806British Heart Foundation RG/08/008/25291British Heart Foundation RG/10/12/28456Chief Scientist Office CZB/4/710Chief Scientist Office CZG/2/513Intramural NIH HHSMedical Research Council G0601653Medical Research Council G1001799Medical Research Council MC_PC_U127561128Medical Research Council MC_PC_U127592696Medical Research Council MC_U147585824Medical Research Council MC_UP_A620_1014Medical Research Council MC_UP_A620_1017Medical Research Council MC_UU_12011/1Medical Research Council MC_UU_12011/4Medical Research Council MC_UU_12019/1Medical Research Council MR/J012165/1Medical Research Council MR/K006584/1Medical Research Council MR/K013351/1NIDDK NIH HHS R01 DK072041Wellcome Trust 098381
6 · The paper itself

Abstract

backgroundLow plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.

methodsIn this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.

findingsIn phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).

interpretationIncreased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

fundingBritish Heart Foundation, UK Medical Research Council, and Academy of Finland.

Indexed as

Polymorphism, Single NucleotideAdultBody Mass IndexCholestanetriol 26-MonooxygenaseCytochrome P450 Family 2FemaleGenetic Predisposition to DiseaseHumansHypertensionMaleMendelian Randomization AnalysisMiddle AgedOxidoreductases Acting on CH-CH Group DonorsPhenotypeRandomized Controlled Trials as TopicVitamin D25-hydroxyvitamin D7-dehydrocholesterol reductaseCholestanetriol 26-MonooxygenaseCYP2R1 protein, humanCytochrome P450 Family 2Oxidoreductases Acting on CH-CH Group DonorsVitamin D

Identifiers

PMID24974252
PMCPMC4582411

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.