Evidence map›Paper›PMID 23028342›Full record

SynthesisPLoS genetics2012

New susceptibility loci associated with kidney disease in type 1 diabetes.

Niina Sandholm, Rany M Salem, Amy Jayne McKnight, Eoin P Brennan, Carol Forsblom, Tamara Isakova, Gareth J McKay, Winfred W Williams, Denise M Sadlier, Ville-Petteri Mäkinen and 83 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 15 pooled it
18.7field-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

146 citing papers in PubMed, 15 syntheses or guidelines pooled it, 281 citations in OpenAlex.

  1. Pooled it
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  7. Genome-wide association study identifiesJournal of medical genetics · 2018
    Pooled it
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  16. Review
  17. Exome-Wide Analysis Identifies a RareKidney international reports · 2026
    Article
  18. Review
  19. Article
  20. Review

86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

93 authors at 20 institutions in 15 countries.

Niina SandholmFolkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.
Rany M Salem
Amy Jayne McKnight
Eoin P Brennan
Carol Forsblom
Tamara Isakova
Gareth J McKay
Winfred W Williams
Denise M Sadlier
Ville-Petteri Mäkinen
Elizabeth J Swan
Cameron Palmer
Andrew P Boright
Emma Ahlqvist
Harshal A Deshmukh
Benjamin J Keller
Huateng Huang
Aila J Ahola
Emma Fagerholm
Daniel Gordin
Valma Harjutsalo
Bing He
Outi Heikkilä
Kustaa Hietala
Janne Kytö
Päivi Lahermo
Markku Lehto
Raija Lithovius
Anne-May Osterholm
Maija Parkkonen
Janne Pitkäniemi
Milla Rosengård-Bärlund
Markku Saraheimo
Cinzia Sarti
Jenny Söderlund
Aino Soro-Paavonen
Anna Syreeni
Lena M Thorn
Heikki Tikkanen
Nina Tolonen
Karl Tryggvason
Jaakko Tuomilehto
Johan Wadén
Geoffrey V Gill
Sarah Prior
Candace Guiducci
Daniel B Mirel
Andrew Taylor
S Mohsen Hosseini
DCCT/EDIC Research Group
Hans-Henrik Parving
Peter Rossing
Lise Tarnow
Claes Ladenvall
François Alhenc-Gelas
Pierre Lefebvre
Vincent Rigalleau
Ronan Roussel
David-Alexandre Tregouet
Anna Maestroni
Silvia Maestroni
Henrik Falhammar
Tianwei Gu
Anna Möllsten
Danut Cimponeriu
Mihai Ioana
Maria Mota
Eugen Mota
Cristian Serafinceanu
Monica Stavarachi
Robert L Hanson
Robert G Nelson
Matthias Kretzler
Helen M Colhoun
Nicolae Mircea Panduru
Harvest F Gu
Kerstin Brismar
Gianpaolo Zerbini
Samy Hadjadj
Michel Marre
Leif Groop
Maria Lajer
Shelley B Bull
Daryl Waggott
Andrew D Paterson
David A Savage
Stephen C Bain
Finian Martin
Joel N Hirschhorn
Catherine Godson
Jose C Florez
Per-Henrik Groop
Alexander P Maxwell
Helsinki University Hospital · FIBroad Institute · USKarolinska Institutet · SEQueen's University Belfast · GBInserm · FRUniversity College Dublin · IEUniversity of Toronto · CALund University · SESteno Diabetes Centers · DKUniversity of Helsinki · FIUniversity of Medicine and Pharmacy of Craiova · ROCarol Davila University of Medicine and Pharmacy · ROKarolinska University Hospital · SESwansea University · GBTranslational Genomics Research Institute · USUniversity of Bucharest · ROUniversity of Dundee · GBUniversity of Michigan · USAarhus University · DKBaker Heart and Diabetes Institute · AU

Funding

Genetic Epidemiology of Diabetic NephropathyZIADK069094 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI HANSON, ROBERT · 2009 to 2025
$7.7M
Genome-wide association of common alleles with long-term diabetic complicationsR01DK077510 · NIDDK · HOSPITAL FOR SICK CHLDRN (TORONTO) · PI PATERSON, ANDREW D · 2006 to 2008
$2.3M
Genome-Wide Association Studies of Diabetic NephropathyR01DK081923 · NIDDK · BROAD INSTITUTE, INC. · PI HIRSCHHORN, JOEL N · 2009 to 2012
$2.3M
EPIDEMIOLOGY OF DIABETES INTERVENTIONS &COMPLICATIONSN01DK062204 · NIDDK · GEORGE WASHINGTON UNIVERSITY · 1996 to 2004
$2.1M
Calcium Handling and Secondary Hyperparathyroidism in Chronic Kidney DiseaseK23DK087858 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ISAKOVA, TAMARA · 2010 to 2014
$845k
CIHRMedical Research Council MR/K003364/1NIDDK NIH HHS K23 DK087858NIDDK NIH HHS N01-DK-6-2204NIDDK NIH HHS R01 DK077510NIDDK NIH HHS R01-DK-077510NIDDK NIH HHS R01 DK081923PHS HHS NIH NIDDK R01 DK081923
6 · The paper itself

Abstract

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Indexed as

Kidney Failure, ChronicDiabetes Mellitus, Type 1Diabetic NephropathiesErbB ReceptorsFibrosisGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansKidney TubulesNuclear ProteinsPolymorphism, Single NucleotideQuantitative Trait LociReceptor, ErbB-4Transforming Growth Factor beta1AFF3 protein, humanERBB4 protein, humanErbB ReceptorsNuclear ProteinsReceptor, ErbB-4Transforming Growth Factor beta1

Identifiers

PMID23028342
PMCPMC3447939
OpenAlexW2036632755

What Socratic 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 Socratic graph.