SynthesisHuman molecular genetics2016
Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
4.5field-weighted citation impact, top 6% of its field
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.
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.
Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nature genetics · 2018Pooled it
- Trans-ethnic meta-regression of genome-wide association studies accounting for ancestry increases power for discovery and improves fine-mapping resolution.Human molecular genetics · 2017Pooled it
- The Effect of Short-Chain Fatty Acids on Growth ofMicroorganisms · 2022Article
- Trans-ancestral dissection of urate- and gout-associated major loci SLC2A9 and ABCG2 reveals primate-specific regulatory effects.Journal of human genetics · 2021Article
- Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure.Nature reviews. Endocrinology · 2020Review
- Cohort profile: the Singapore diabetic cohort study.BMJ open · 2020Article
- Mechanisms of Type 2 Diabetes Risk Loci.Current diabetes reports · 2017Review
- Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations.Diabetes & metabolism · 2017Article
- CDK5 Regulatory Subunit-Associated Protein 1-like 1 Negatively Regulates Adipocyte Differentiation through Activation of Wnt Signaling Pathway.Scientific reports · 2017Article
- Physical Interactions and Expression Quantitative Traits Loci Identify Regulatory Connections for Obesity and Type 2 Diabetes Associated SNPs.Frontiers in genetics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
59 authors at 20 institutions in 11 countries.
Momoko HorikoshiWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Lorenzo PasqualiProgram of Predictive and Personalized Medicine of Cancer (PMPPC), Germans Trias i Pujol University Hospital and Research Institute, Badalona, Spain, Josep Carreras Leukaemia Research Institute, Badalona, Spain, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
Steven WiltshireWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Jeroen R HuygheDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Anubha MahajanWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Jennifer L AsimitDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
Teresa FerreiraWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Adam E LockeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Neil R RobertsonWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Xu WangSaw Swee Hock School of Public Health.
Xueling SimDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA, Saw Swee Hock School of Public Health.
Hayato FujitaDepartment of Diabetes and Endocrinology, JR Tokyo General Hospital, Tokyo, Japan.
Kazuo HaraDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine and.
Robin YoungDepartment of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.
Weihua ZhangDepartment of Cardiology, Ealing Hospital NHS Trust, Southall, Middlesex, UK, Department of Epidemiology and Biostatistics.
Sungkyoung ChoiInterdisciplinary Program in Bioinformatics and.
Han ChenDepartment of Biostatistics, Harvard School of Public Health, Boston, MA, USA, Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Ismeet KaurGenomics and Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, New Delhi, India.
Fumihiko TakeuchiDepartment of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Pierre FontanillasProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Dorothée ThuillierIntegrative Genomics and Modelization of Metabolic Diseases CNRS UMR8199, Lille Institute of Biology, E.G.I.D - FR3508 European Genomics Institute of Diabetes, Lille, France.
Loic YengoIntegrative Genomics and Modelization of Metabolic Diseases CNRS UMR8199, Lille Institute of Biology, E.G.I.D - FR3508 European Genomics Institute of Diabetes, Lille, France.
Jennifer E BelowHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Claudia H T TamDepartment of Medicine and Therapeutics.
Ying Wu
Gonçalo AbecasisDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
David AltshulerProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA, Department of Genetics and Department of Medicine, Harvard Medical School, Boston, MA, USA, Department of Molecular Biology, Diabetes Research Center (Diabetes Unit), Department of Medicine.
Graeme I BellDepartments of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA.
John BlangeroDepartment of Genetics, Texas Biomedical Research Institute, Houston, TX, USA.
Noél P BurttProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Ravindranath DuggiralaDepartment of Genetics, Texas Biomedical Research Institute, Houston, TX, USA.
Jose C FlorezProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA, Diabetes Research Center (Diabetes Unit), Department of Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA, Center for Human Genetic Research, Department of Medicine, and.
Craig L HanisHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Mark SeielstadBlood Systems Research Institute, San Francisco, CA, USA, Department of Laboratory Medicine and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Gil AtzmonDepartment of Natural Science, University of Haifa, Haifa, Israel, Departments of Medicine and Genetics, Albert Einstein College of Medicine, New York, USA.
Juliana C N ChanDepartment of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
Ronald C W MaDepartment of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
Philippe FroguelDepartment of Genomics of Common Disease, School of Public Health, Integrative Genomics and Modelization of Metabolic Diseases CNRS UMR8199, Lille Institute of Biology, E.G.I.D - FR3508 European Genomics Institute of Diabetes, Lille, France.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
Dwaipayan BharadwajGenomics and Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, New Delhi, India, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
Josee 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.
James B MeigsDepartment of Medicine, Harvard Medical School, Boston, MA, USA, General Medicine Division, Massachusetts General Hospital, Boston, MA, USA.
Yoon Shin ChoDepartment of Biomedical Science, Hallym University, Chuncheon, Republic of Korea.
Taesung ParkInterdisciplinary Program in Bioinformatics and Department of Statistics, Seoul National University, Seoul, Republic of Korea.
Jaspal S KoonerDepartment of Cardiology, Ealing Hospital NHS Trust, Southall, Middlesex, UK, National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College Healthcare NHS Trust, and.
John C ChambersDepartment of Cardiology, Ealing Hospital NHS Trust, Southall, Middlesex, UK, Department of Epidemiology and Biostatistics, Imperial College Healthcare NHS Trust, and.
Danish SaleheenDepartment of Biostatistics and Epidemiology, Center for Non-Communicable Diseases, University of Pennsylvania, Philadelphia, PA, USA.
Takashi KadowakiDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine and Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, Japan.
E Shyong TaiSaw Swee Hock School of Public Health, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore, Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School Singapore, Singapore.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Nancy J CoxSchool of Medicine, Vanderbilt University, Nashville, TN, USA.
Jorge FerrerCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain, Genomic Programming of Beta-cells Laboratory, Institut d'Investigacions August Pi i Sunyer (IDIBAPS), Barcelona, Spain, Department of Medicine, Imperial College London, London, UK.
Eleftheria ZegginiDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
Norihiro KatoDepartment of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Yik Ying TeoSaw Swee Hock School of Public Health, Life Sciences Institute and Department of Statistics and Applied Probability, National University of Singapore, Singapore.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Mark I McCarthyWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK, Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK and.
Andrew P MorrisWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK, Department of Biostatistics, University of Liverpool, Liverpool, UK a.p.morris@liverpool.ac.uk.
T2D-GENES Consortium
University of Oxford · GBBroad Institute · USUniversity of Michigan–Ann Arbor · USCentre for Human Genetics · GBHarvard University · USNational Center for Global Health and Medicine · JPNational University of Singapore · SGStatistical Research (United States) · USTexas Biomedical Research Institute · USTherapeutics Clinical Research · USThe University of Texas Health Science Center at Houston · USUniversity of North Carolina at Chapel Hill · USWellcome Sanger Institute · GBAlbert Einstein College of Medicine · USBoston University · USCancer Research And Biostatistics · USCentre National de la Recherche Scientifique · FRChinese University of Hong Kong · CNConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESDiabetes Australia · AU
Funding
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7MTRANSGENIC COREP60DK020595 · NIDDK · UNIVERSITY OF CHICAGO · PI BELL, GRAEME I · 1985 to 2012
$25.5MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MPilot and Feasibility ProgramP30DK020595 · NIDDK · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2013 to 2026
$20.9MMultiethnic Study of Type 2 Diabetes GenesU01DK085526 · NIDDK · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, JABLONSKI, KATHLEEN ANN · 2009 to 2014
$15.7MIdentifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6MTargeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3MEinstein's Nathan Shock Center of Excellence in Basic Biology of AgingP30AG038072 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI HUFFMAN, DEREK MAJOR · 2010 to 2024
$10.8MSTATISTICS AND DATA MANAGEMENT COREP01AG027734 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI MORROW, BERNICE E · 2007 to 2012
$9.3MGenetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2MIdentifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7MDiscovery of Functional Variants in Type 2 Diabetes Genes in Mexican AmericansU01DK085524 · NIDDK · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI BLANGERO, JOHN, DEFRONZO, RALPH A · 2009 to 2019
$5.9MBritish Heart Foundation SP/04/002Department of Health RP-PG-0407-10371Medical Research Council G0601261Medical Research Council G0601966Medical Research Council G0700931Medical Research Council MR/K021486/1NHGRI NIH HHS R01 HG000376NHGRI NIH HHS R56 HG000376NHGRI NIH HHS U01 HG005773NHLBI NIH HHS HHSN268201300046CNHLBI NIH HHS HHSN268201300047CNHLBI NIH HHS HHSN268201300048CNHLBI NIH HHS HHSN268201300049CNHLBI NIH HHS HHSN268201300050CNHLBI NIH HHS R01 HL102830NIA NIH HHS P01 AG027734NIA NIH HHS P30 AG038072NIA NIH HHS R01 AG028872NIA NIH HHS R01 AG042188NIA NIH HHS R01 AG046949NIDDK NIH HHS K24 DK080140NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK020595NIDDK NIH HHS P60 DK020595NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK073541NIDDK NIH HHS R01 DK078616NIDDK NIH HHS R01 DK093757NIDDK NIH HHS U01 DK062370NIDDK NIH HHS U01 DK078616NIDDK NIH HHS U01 DK085501NIDDK NIH HHS U01 DK085524NIDDK NIH HHS U01 DK085526NIDDK NIH HHS U01 DK085545NIDDK NIH HHS U01 DK085584NIDDK NIH HHS U01 DK105535NIMH NIH HHS R01 MH090937NIMH NIH HHS R01 MH101820Wellcome TrustWellcome Trust WT084723Wellcome Trust WT090532Wellcome Trust WT098017Wellcome Trust WT098051
Abstract
To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci.
Indexed as
Chromosome MappingGenetic Association StudiesGenetic Predisposition to DiseaseAllelesAsian PeopleBlack or African AmericanCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18Diabetes Mellitus, Type 2FemaleHumansKCNQ1 Potassium ChannelLinkage DisequilibriumMalePolymorphism, Single NucleotideRegulatory Elements, TranscriptionalCDKAL1 protein, humanCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18IGF2BP2 protein, humanKCNQ1 Potassium ChannelKCNQ1 protein, humanRNA-Binding ProteinstRNA Methyltransferases
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
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 OpenQuestion graph.