Evidence map›Paper›PMID 30297969›Full record

ArticleNature genetics2018

Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.

Anubha Mahajan, Daniel Taliun, Matthias Thurner, Neil R Robertson, Jason M Torres, N William Rayner, Anthony J Payne, Valgerdur Steinthorsdottir, Robert A Scott, Niels Grarup and 105 more

2 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1,118 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,118citing papers in PubMed, 14 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.

NCT04331535 naunknown statusnot on this mapstarted 2020, after this paper: background citation

Pragmatic Randomized Trial of Polygenic Risk Scoring for Common Diseases in Primary Care

TypeinterventionalSponsorBoston VA Research Institute, Inc.Ran2020 to 2025Enrolled1,076ConditionsCoronary Artery Disease, Atrial Fibrillation, Type 2 Diabetes, Colorectal CancerArmsPolygenic risk score (PRS)
NCT05166447 enrolling by invitationnot on this mapstarted 2021, after this paper: background citation

Twenty-year Follow-up of the Inter99 Cohort

TypeobservationalSponsorBispebjerg HospitalRan2021 to 2028Enrolled4,000ConditionsCoronary Heart Disease, Acute Myocardial Infarction, Cardiovascular Diseases, Type 2 Diabetes
3 · Its place in the literature

Who cites it

1,118 citing papers in PubMed, 14 syntheses or guidelines pooled it.

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  16. Impact of Genetics on Endocrine Manifestations of Cystic Fibrosis.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2026
    Review
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1,058 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

115 authors.

Anubha MahajanWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. anubha@well.ox.ac.uk.ORCID http://orcid.org/0000-0001-5585-3420
Daniel TaliunDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Matthias ThurnerWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Neil R RobertsonWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Jason M TorresWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
N William RaynerWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Anthony J PayneWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Valgerdur SteinthorsdottirdeCODE Genetics, Amgen Inc., Reykjavik, Iceland.
Robert A ScottMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
James P CookDepartment of Biostatistics, University of Liverpool, Liverpool, UK.
Ellen M SchmidtDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Matthias WuttkeInstitute of Genetic Epidemiology, Department of Biometry, Epidemiology, and Medical Bioinformatics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
Chloé SarnowskiDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Reedik MägiEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Jana NanoDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Christian GiegerResearch Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.
Stella TrompetSection of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Cécile LecoeurCNRS-UMR8199, Lille University, Lille Pasteur Institute, Lille, France.
Michael H PreussCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bram Peter PrinsDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Xiuqing GuoDepartment of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Lawrence F BielakDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Jennifer E BelowVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Donald W BowdenCenter for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
John Campbell ChambersDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.
Young Jin KimDivision of Genome Research, Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
Maggie C Y NgCenter for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Lauren E PettyVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Xueling SimSaw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
Weihua ZhangDepartment of Epidemiology and Biostatistics, Imperial College London, London, UK.
Amanda J BennettOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Jette Bork-JensenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Chad M BrummettDepartment of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA.
Mickaël CanouilCNRS-UMR8199, Lille University, Lille Pasteur Institute, Lille, France.
Kai-Uwe Ec KardtDepartment of Nephrology and Medical Intensive Care and German Chronic Kidney Disease Study, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Krista FischerEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Florian KronenbergDivision of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Kristi LällEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Ching-Ti LiuDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Adam E LockeMcDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
Jian'an LuanMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Ioanna NtallaWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Vibe NylanderOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Sebastian SchönherrDivision of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Claudia SchurmannCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Loïc YengoCNRS-UMR8199, Lille University, Lille Pasteur Institute, Lille, France.
Erwin P BottingerCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ivan BrandslundInstitute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
Cramer ChristensenMedical Department, Lillebælt Hospital Vejle, Vejle, Denmark.
George DedoussisDepartment of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece.
Jose C FlorezDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Ian FordRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Oscar H FrancoDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Timothy M FraylingGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Vilmantas GiedraitisDepartment of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.
Sophie HackingerDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Andrew T HattersleyUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Christian HerderGerman Center for Diabetes Research (DZD), Neuherberg, Germany.
M Arfan IkramDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Martin IngelssonDepartment of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.
Marit E JørgensenSteno Diabetes Center Copenhagen, Gentofte, Denmark.
Torben JørgensenResearch Centre for Prevention and Health, Capital Region of Denmark, Glostrup, Denmark.
Jennifer KriebelResearch Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.
Johanna KuusistoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Symen LigthartDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Cecilia M LindgrenWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Allan LinnebergResearch Centre for Prevention and Health, Capital Region of Denmark, Glostrup, Denmark.
Valeriya LyssenkoDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.
Vasiliki MamakouDromokaiteio Psychiatric Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Thomas MeitingerInstitute of Human Genetics, Technische Universität München, Munich, Germany.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Andrew D MorrisClinical Research Centre, Centre for Molecular Medicine, Ninewells Hospital and Medical School, Dundee, UK.
Girish NadkarniDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
James S PankowDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Annette PetersGerman Center for Diabetes Research (DZD), Neuherberg, Germany.
Naveed SattarInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Alena StančákováInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Kent D TaylorDepartment of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Barbara ThorandGerman Center for Diabetes Research (DZD), Neuherberg, Germany.
Gudmar ThorleifssondeCODE Genetics, Amgen Inc., Reykjavik, Iceland.
Unnur ThorsteinsdottirdeCODE Genetics, Amgen Inc., Reykjavik, Iceland.
Jaakko TuomilehtoDepartment of Health, National Institute for Health and Welfare, Helsinki, Finland.
Daniel R WitteDepartment of Public Health, Aarhus University, Aarhus, Denmark.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Eleftheria ZegginiDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Ruth J F LoosCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Philippe FroguelCNRS-UMR8199, Lille University, Lille Pasteur Institute, Lille, France.
Erik IngelssonDivision of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Lars LindDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Leif GroopDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Francis S CollinsGenome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Colin N A PalmerPat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Harald GrallertResearch Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.
Andres MetspaluEstonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Abbas DehghanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Anna KöttgenInstitute of Genetic Epidemiology, Department of Biometry, Epidemiology, and Medical Bioinformatics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
Goncalo R AbecasisDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
James B MeigsDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Jerome I RotterDepartment of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Jonathan MarchiniWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Claudia LangenbergMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Nicholas J WarehamMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Kari StefanssondeCODE Genetics, Amgen Inc., Reykjavik, Iceland.
Anna L GloynWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Andrew P MorrisWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-6805-6014
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-6442-7754
Mark I McCarthyWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. mark.mccarthy@drl.ox.ac.uk.ORCID http://orcid.org/0000-0002-4393-0510

Funding

Genetic analysis of type II diabetes in Finnish populationZIAHG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ERDOS, MICHAEL · 2009 to 2025
$38.2M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Scott Soleimanpour · 2013 to 2026
$24.3M
Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Identifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6M
Targeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3M
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
Genetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2M
Genetics of African American Type 2 DiabetesR01DK066358 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI NG, MAGGIE · 2003 to 2019
$6.2M
Common Genetic Variation and Quantitative Diabetes TraitsR01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2008 to 2014
$5.0M
Rare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6M
Genetic Determinants of Adiposity in African AmericansR01DK087914 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI NG, MAGGIE · 2010 to 2014
$3.0M
Genetic Mechanisms of Arteriosclerosis in Hypertensive SibshipsR01HL119443 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARDIA, SHARON L · 2014 to 2017
$2.1M
Medical Research Council G0601261Medical Research Council MC_UU_12015/1NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL119443NIA NIH HHS K99 AG066849NIDDK NIH HHS K24 DK080140NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK066358NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK078616NIDDK NIH HHS R01 DK087914NIDDK NIH HHS R01 DK093757NIDDK NIH HHS U01 DK062370NIDDK NIH HHS U01 DK078616NIDDK NIH HHS U01 DK105535NIDDK NIH HHS U01 DK105556Wellcome Trust 098381Wellcome Trust 200837/Z/16/Z
6 · The paper itself

Abstract

We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%, 14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).

Indexed as

Epigenesis, GeneticPolymorphism, Single NucleotideBody Mass IndexCase-Control StudiesChromosome MappingDiabetes Mellitus, Type 2FemaleGene FrequencyGenetic LociGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHigh-Throughput Screening AssaysHumansIslets of LangerhansLinkage Disequilibrium

Identifiers

PMID30297969
PMCPMC6287706

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.