Evidence map›Paper›PMID 28757204›Full record

SynthesisAmerican journal of human genetics2017

Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis.

Despoina Manousaki, Tom Dudding, Simon Haworth, Yi-Hsiang Hsu, Ching-Ti Liu, Carolina Medina-Gómez, Trudy Voortman, Nathalie van der Velde, Håkan Melhus, Cassianne Robinson-Cohen and 43 more

Erratum issuedOpen access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 3 pooled it
16.5field-weighted citation impact, top 1% of its field
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

74 citing papers in PubMed, 3 syntheses or guidelines pooled it, 136 citations in OpenAlex.

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  17. Effective counseling for children's bone health.Journal of the Pediatric Orthopaedic Society of North America · 2024
    Article
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

53 authors at 20 institutions in 6 countries.

Despoina ManousakiDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada.
Tom DuddingMedical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
Simon HaworthMedical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
Yi-Hsiang HsuInstitute for Aging Research, Hebrew SeniorLife, Boston, MA 02131, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Boston, MA 02142, USA.
Ching-Ti LiuDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Carolina Medina-GómezDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Generation R Study Group, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Trudy VoortmanGeneration R Study Group, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Nathalie van der VeldeDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Section of Geriatrics, Department of Internal Medicine, Academic Medical Center, Amsterdam 1105 AZ, the Netherlands.
Håkan MelhusDepartment of Medical Sciences, Uppsala University, Uppsala 751 85, Sweden.
Cassianne Robinson-CohenKidney Research Institute, Division of Nephrology, University of Washington, Seattle, WA 98195, USA.
Diana L CousminerDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Maria NethanderCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden; Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg 41390, Sweden.
Liesbeth VandenputCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden.
Raymond NoordamSection of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Vincenzo ForgettaDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada.
Celia M T GreenwoodDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada; Department of Oncology, McGill University, Montreal, QC H4A 3T2, Canada.
Mary L BiggsCardiovascular Health Research Unit, Departments of Medicine and Biostatistics, University of Washington, Seattle, WA 98101, USA.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA 98101, USA; Kaiser Permanente Washington Health Research Unit, Seattle, WA 98101, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Babette S ZemelDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Jonathan A MitchellDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Bruce TaylorMenzies Institute for Medical Research University of Tasmania, Locked Bag 23, Hobart, Tasmania 7000, Australia.
Mattias LorentzonCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden; Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 43180 Mölndal, Sweden; Geriatric Medicine, Sahlgrenska University Hospital, 43180 Mölndal, Sweden.
Magnus KarlssonClinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, 22241 Malmö, Sweden; Department of Orthopaedics, Skåne University Hospital, 22241 Malmö, Sweden.
Vincent V W JaddoeGeneration R Study Group, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Henning TiemeierGeneration R Study Group, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Natalia Campos-ObandoDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Oscar H FrancoDepartment of Epidemiology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Andre G UtterlindenDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Generation R Study Group, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Linda BroerDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Natasja M van SchoorDepartment of Epidemiology and Biostatistics and EMGO Institute of Health and Care Research, VU University Medical Center, Amsterdam 1081 HV, the Netherlands.
Annelies C HamDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
M Arfan IkramDepartment of Epidemiology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
David KarasikInstitute for Aging Research, Hebrew SeniorLife, Boston, MA 02131, USA.
Renée de MutsertDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Frits R RosendaalDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Martin den HeijerDepartment of Endocrinology, VU University Medical Center, Amsterdam 1081 HV, the Netherlands.
Thomas J WangDivision of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Lars LindDepartment of Medical Sciences, Uppsala University, Uppsala 751 85, Sweden.
Eric S OrwollBone and Mineral Unit, Oregon Health & Science University, Portland, OR 97239, USA; Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Karl MichaëlssonDepartment of Surgical Sciences, Uppsala University, 75105 Uppsala, Sweden.
Bryan KestenbaumKidney Research Institute, Division of Nephrology, University of Washington, Seattle, WA 98195, USA.
Claes OhlssonCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden.
Dan MellströmCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden; Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 43180 Mölndal, Sweden.
Lisette C P G M de GrootDivision of Human Nutrition, Wageningen University, Wageningen 6708 WE, the Netherlands.
Struan F A GrantDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Douglas P KielInstitute for Aging Research, Hebrew SeniorLife, Boston, MA 02131, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Boston, MA 02142, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
M Carola ZillikensDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Generation R Study Group, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015 GE, the Netherlands.
Stephen SawcerDepartment of Clinical Neurosciences, University of Cambridge, Box 165, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK.
Nicholas J TimpsonMedical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
J Brent RichardsDepartment of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada; Department of Twin Research and Genetic Epidemiology, King's College London, London WC2R 2LS, UK; Department of Medicine, McGill University, Montreal, QC H3G 1Y6, Canada. Electronic address: brent.richards@mcgill.ca.
Erasmus MC · NLLeiden University Medical Center · NLUniversity of Gothenburg · SEUniversity of Washington · USMedical Research Council · GBUniversity of Pennsylvania · USUppsala University · SEHebrew SeniorLife · USJewish General Hospital · CAMcGill University · CAAmsterdam UMC Location VUmc · NLBeth Israel Deaconess Medical Center · USBoston University · USChildren's Hospital of Philadelphia · USEMGO Institute for Health and Care Research · NLLund University · SEOregon Health & Science University · USSahlgrenska University Hospital · SEUCLA Medical Center · USUniversity of Cambridge · GB

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
CHS research resources for the cardiovascular health of older adultsU01HL130114 · NHLBI · UNIVERSITY OF WASHINGTON · PI BURKE, GREGORY L, KRONMAL, RICHARD A · 2016 to 2019
$6.6M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
Sleep, Energetic Behaviors, and Adolescent Obesity during the Transition from Middle to High SchoolK01HL123612 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI MITCHELL, JONATHAN ANDREW · 2015 to 2019
$787k
Cancer Research UK 19169European Research Council 648916Medical Research Council G0701603Medical Research Council MC_UU_12013/3NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR002369NHLBI NIH HHS K01 HL123612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL130114Wellcome Trust 202802/Z/16/Z
6 · The paper itself

Abstract

Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10

Indexed as

Cholestanetriol 26-MonooxygenaseCytochrome P450 Family 2Gene FrequencyGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHumansMultiple SclerosisPolymorphism, Single NucleotideRisk FactorsVitamin DVitamin D Deficiency25-hydroxyvitamin DCholestanetriol 26-MonooxygenaseCYP2R1 protein, humanCytochrome P450 Family 2Vitamin DGWASlow-frequency genetic variantsmultiple sclerosisvitamin D

Identifiers

PMID28757204
PMCPMC5544392
OpenAlexW2737599529

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.