Evidence map›Paper›PMID 32077919›Full record

SynthesisCardiovascular research2021

Genome-wide association study on coronary artery disease in type 1 diabetes suggests beta-defensin 127 as a risk locus.

Anni A V Antikainen, Niina Sandholm, David-Alexandre Trégouët, Romain Charmet, Amy Jayne McKnight, Tarunveer S Ahluwalia, Anna Syreeni, Erkka Valo, Carol Forsblom, Daniel Gordin and 5 more

Open access · bronzeAbstract readMeta-Analysis
In one paragraph

Synthesis in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 7% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
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  3. Article
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  5. Review
  6. Article
  7. Review
  8. Article
  9. Mechanisms and regulation of defensins in host defense.Signal transduction and targeted therapy · 2023
    Review
  10. Article
  11. Article
  12. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 6 countries.

Anni A V AntikainenFolkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
Niina SandholmFolkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
David-Alexandre TrégouëtSorbonne Université, UPMC Univ Paris 06, INSERM UMR_S 1166, Paris, France.
Romain CharmetSorbonne Université, UPMC Univ Paris 06, INSERM UMR_S 1166, Paris, France.
Amy Jayne McKnightCentre for Public Health, Queens University of Belfast, Northern Ireland BT7 1NN, UK.
Tarunveer S AhluwaliaSteno Diabetes Center Copenhagen, DK 2820 Gentofte, Denmark.
Anna SyreeniFolkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
Erkka ValoFolkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
Carol ForsblomFolkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
Daniel GordinFolkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
Valma HarjutsaloFolkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
Samy HadjadjDepartment of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Alexander P MaxwellCentre for Public Health, Queens University of Belfast, Northern Ireland BT7 1NN, UK.
Peter RossingSteno Diabetes Center Copenhagen, DK 2820 Gentofte, Denmark.
Per-Henrik GroopFolkhälsan Institute of Genetics, Folkhälsan Research Center, FI-00290 Helsinki, Finland.
University of Helsinki · FIInserm · FRQueen's University Belfast · GBCentre National de la Recherche Scientifique · FRJoslin Diabetes Center · USSteno Diabetes Centers · DKUniversity of Copenhagen · DK

Funding

Integrative genomic, epigenetic and functional studies in diabetic kidney diseaseR01DK105154 · NIDDK · BROAD INSTITUTE, INC. · PI FLOREZ, JOSE CARLOS, HIRSCHHORN, JOEL N · 2016 to 2019
$3.0M
Medical Research CouncilNIDDK NIH HHS R01 DK105154
6 · The paper itself

Abstract

aimsDiabetes is a known risk factor for coronary artery disease (CAD). There is accumulating evidence that CAD pathogenesis differs for individuals with type 1 diabetes (T1D). However, the genetic background has not been extensively studied. We aimed to discover genetic loci increasing CAD susceptibility, especially in T1D, to examine the function of these discoveries and to study the role of the known risk loci in T1D. METHODS AND

resultsWe performed the largest genome-wide association study to date for CAD in T1D, comprising 4869 individuals with T1D (cases/controls: 941/3928). Two loci reached genome-wide significance, rs1970112 in CDKN2B-AS1 [odds ratio (OR) = 1.32, P = 1.50 × 10-8], and rs6055069 on DEFB127 promoter (OR = 4.17, P = 2.35 × 10-9), with consistent results in survival analysis. The CDKN2B-AS1 variant replicated (P = 0.04) when adjusted for diabetic kidney disease in three additional T1D cohorts (cases/controls: 434/3123). Furthermore, we explored the function of the lead discoveries with a cardio-phenome-wide analysis. Among the eight suggestive loci (P < 1 × 10-6), rs70962766 near B3GNT2 associated with central blood pressure, rs1344228 near CNTNAP5 with intima media thickness, and rs2112481 on GRAMD2B promoter with serum leucocyte concentration. Finally, we calculated genetic risk scores for individuals with T1D with the known susceptibility loci. General population risk variants were modestly but significantly associated with CAD also in T1D (P = 4.21 × 10-7).

conclusionWhile general population CAD risk loci had limited effect on the risk in T1D, for the first time, variants at the CDKN2B-AS1 locus were robustly associated with CAD in individuals with T1D. The novel finding on β-defensin DEFB127 promoter provides a link between diabetes, infection susceptibility, and CAD, although pending on future confirmation.

Indexed as

Polymorphism, Single NucleotideAdultAgedbeta-DefensinsCase-Control StudiesCoronary Artery DiseaseDiabetes Mellitus, Type 1FemaleFinlandGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPhenotypebeta-DefensinsCDKN2B antisense RNA, humanDEFB127 protein, humanRNA, Long NoncodingCardiovascular diseaseCoronary artery diseaseGeneticsGenome-wide association studyType 1 diabetes

Identifiers

PMID32077919
PMCPMC8453280
OpenAlexW3007141561

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.