Evidence map›Paper›PMID 32944759›Full record

SynthesisThe Journal of clinical endocrinology and metabolism2021

Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity.

Harshal A Deshmukh, Anne Lundager Madsen, Ana Viñuela, Christian Theil Have, Niels Grarup, Andrea Tura, Anubha Mahajan, Alison J Heggie, Robert W Koivula, Federico De Masi and 24 more

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

Synthesis in The Journal of clinical endocrinology and metabolism, 2021. 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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 16 institutions in 9 countries.

Harshal A DeshmukhTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Anne Lundager MadsenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Ana ViñuelaDepartment of Genetic Medicine and Development, University of Geneva Medical School, Geneva.
Christian Theil HaveNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Andrea TuraInstitute of Neuroscience, National Research Council, Corso Stati Uniti 4, Padua, Italy.
Anubha MahajanWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Alison J HeggieTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Robert W KoivulaOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Federico De MasiIntegrative Systems Biology Group, Department of Health Technology, Technical University of Denmark (DTU), Kemitorvet, Building 208, 2800 Kgs. Lyngby, Denmark.
Konstantinos K TsirigosIntegrative Systems Biology Group, Department of Health Technology, Technical University of Denmark (DTU), Kemitorvet, Building 208, 2800 Kgs. Lyngby, Denmark.
Allan LinnebergCenter for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
Thomas DrivsholmCenter for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Thorkild I A SørensenNovo Nordisk Foundation Centre for Basic Metabolic Research (Section of Metabolic Genetics), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Arne AstrupDepartment of Nutrition, Exercise and Sports (NEXS), Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Anette A P GjesingNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Imre PavoEli Lilly Regional Operations Ges.m.b.H., Koelblgasse 8-10, Vienna, Austria.
Andrew R WoodGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Hartmut RuettenDiabetes Division, Sanofi-Aventis Deutschland GmbH, Frankfurt, 65926 Frankfurt am Main, Germany.
Angus G JonesNIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK.
Anitra D M KoopmanDepartment of Epidemiology and Biostatistics, VUMC, de Boelelaan 1089a, HV, Amsterdam, the Netherlands.
Henna CederbergDepartment of Endocrinology, Abdominal Centre, Helsinki University Hospital, Helsinki, Finland.
Femke RuttersDepartment of Epidemiology and Biostatistics, VUMC, de Boelelaan 1089a, HV, Amsterdam, the Netherlands.
Martin RidderstraleDepartment of Clinical Sciences, Diabetes & Endocrinology Unit, Lund University, Skåne University Hospital Malmö, CRC, 91-12, 205 02, Malmö, Sweden.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Mark I McCarthyOxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Tim M FraylingGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
Ele FerranniniCNR Institute of Clinical Physiology, Pisa, Italy.
Paul W FranksOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Ewan R PearsonDivision of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK.
Andrea MariInstitute of Neuroscience, National Research Council, Corso Stati Uniti 4, Padua, Italy.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Mark WalkerTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
University of Copenhagen · DKNewcastle University · GBUniversity of Exeter · GBLund University · SENational Research Council · ITTechnical University of Denmark · DKVrije Universiteit Amsterdam · NLCentre for Human Genetics · GBHarvard University · USHelsinki University Hospital · FIIstituto di Fisiologia Clinica · ITSanofi (Germany) · DEUniversity of Dundee · GBUniversity of Eastern Finland · FIUniversity of Geneva · CHUniversity of Oxford · GB

Funding

Wellcome TrustWellcome Trust 102820/Z/13/Z
6 · The paper itself

Abstract

contextPancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity.

objectiveTo understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies.

designWe performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models.

resultsBeta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10-9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10-9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity.

conclusionWe show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.

Indexed as

AdultAgedCase-Control StudiesCohort StudiesDiabetes Mellitus, Type 2FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGlucoseGlucose IntoleranceGlucose Tolerance TestHumansInsulin-Secreting CellsInsulin SecretionMaleMiddle AgedGlucosebeta-cell functiondiabetes progressionGlucose intoleranceincretinmathematical model

Identifiers

PMID32944759
PMCPMC7765651
OpenAlexW3087077297

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.