New susceptibility loci associated with kidney disease in type 1 diabetes

Show simple item record Sandholm, Niina Salem, Rany M. McKnight, Amy Jayne Brennan, Eoin P. Forsblom, Carol Isakova, Tamara McKay, Gareth J. Williams, Winfred W. Sadlier, Denise M. Mäkinen, Ville-Petteri Swan, Elizabeth J. Palmer, Cameron Boright, Andrew P. Ahlqvist, Emma Deshmukh, Harshal A. Keller, Benjamin J. Huang, Huateng Ahola, Aila Dahlström, Emma Helena Gordin, Ted Daniel Harjutsalo, Valma He, Bing Heikkilä, Outi Hietala, Kustaa Kytö, Janne Lahermo, Päivi Lehto, Markku Lithovius, Raija Österholm, Anne-May Parkkonen, Maija Pitkäniemi, Janne Mikael Rosengård-Bärlund, Milla Saraheimo, Markku Sarti, Cinzia Söderlun, Jenny Soro-Paavonen, Aino Syreeni, Anna Thorn, Lena Tikkanen, Heikki Olavi Tolonen, Nina Emilia Tryggvason, Karl Tuomilehto, Jaakko Waden, Johan Gill, Geoffrey V. Prior, Sarah Guiducci, Candace Mirel, Daniel B. Taylor, Andrew Hosseini, S. Mohsen EDIC Research Group, DCCT/ Parving, Hans-Henrik Rossing, Peter Tarnow, Lise Ladenvall, Claes Alhenc-Gelas, Francois Lefebvre, Pierre Rigalleau, Vincent Roussel, Ronan Tregouet, David-Alexandre Maestroni, Anna Falhammar, Henrik Gu, Tianwei Möllsten, Anna Cimponeriu, Danut Ioana, Mihai Mota, Maria Mota, Eugen Serafinceanu, Cristian Stavarachi, Monica Hanson, Robert L. Nelson, Robert G. Kretzler, Matthias Colhoun, Helen M. Panduru, Nicolae Mircea Gu, Harvest F. Brismar, Kerstin Zerbini, Gianpaolo Hadjadj, Samy Marre, Michel Groop, Leif Lajer, Maria Bull, Shelley B. Waggott, Daryl Paterson, Andrew D. Savage, David A. Bain, Stephen C. Martin, Finian Hirschhorn, Joel N. Godson, Catherine Florez, Jose C. Groop, Per Henrik Maxwell, Alexander P. Panduru, Nicolae Mircea 2016-05-20T08:36:01Z 2016-05-20T08:36:01Z 2012
dc.identifier.citation Sandholm , N , Salem , R M , McKnight , A J , Brennan , E P , Forsblom , C , Isakova , T , McKay , G J , Williams , W W , Sadlier , D M , Mäkinen , V-P , Swan , E J , Palmer , C , Boright , A P , Ahlqvist , E , Deshmukh , H A , Keller , B J , Huang , H , Ahola , A , Dahlström , E H , Gordin , T D , Harjutsalo , V , He , B , Heikkilä , O , Hietala , K , Kytö , J , Lahermo , P , Lehto , M , Lithovius , R , Österholm , A-M , Parkkonen , M , Pitkäniemi , J M , Rosengård-Bärlund , M , Saraheimo , M , Sarti , C , Söderlun , J , Soro-Paavonen , A , Syreeni , A , Thorn , L , Tikkanen , H O , Tolonen , N E , Tryggvason , K , Tuomilehto , J , Waden , J , Gill , G V , Prior , S , Guiducci , C , Mirel , D B , Taylor , A , Hosseini , S M , EDIC Research Group , DCCT , Parving , H-H , Rossing , P , Tarnow , L , Ladenvall , C , Alhenc-Gelas , F , Lefebvre , P , Rigalleau , V , Roussel , R , Tregouet , D-A , Maestroni , A , Falhammar , H , Gu , T , Möllsten , A , Cimponeriu , D , Ioana , M , Mota , M , Mota , E , Serafinceanu , C , Stavarachi , M , Hanson , R L , Nelson , R G , Kretzler , M , Colhoun , H M , Panduru , N M , Gu , H F , Brismar , K , Zerbini , G , Hadjadj , S , Marre , M , Groop , L , Lajer , M , Bull , S B , Waggott , D , Paterson , A D , Savage , D A , Bain , S C , Martin , F , Hirschhorn , J N , Godson , C , Florez , J C , Groop , P H , Maxwell , A P & Panduru , N M 2012 , ' New susceptibility loci associated with kidney disease in type 1 diabetes ' , PLoS Genetics , vol. 8 , no. 9 , pp. e1002921 .
dc.identifier.other PURE: 24043077
dc.identifier.other PURE UUID: 124dcde6-a12a-4c8b-a81a-39bdddb5b5b9
dc.identifier.other WOS: 000309817900008
dc.identifier.other Scopus: 84866889255
dc.identifier.other ORCID: /0000-0003-3999-0390/work/40217145
dc.identifier.other ORCID: /0000-0003-1494-8292/work/40502846
dc.identifier.other ORCID: /0000-0003-4322-6942/work/44718037
dc.identifier.other ORCID: /0000-0003-1271-8696/work/68617905
dc.description WOS:000309817900008
dc.description.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. en
dc.format.extent 24
dc.language.iso eng
dc.relation.ispartof PLoS Genetics
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3142 Public health care science, environmental and occupational health
dc.subject type 1 diabetes
dc.subject kideny disease
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title New susceptibility loci associated with kidney disease in type 1 diabetes en
dc.type Article
dc.contributor.organization Department of Medicine
dc.contributor.organization Nefrologian yksikkö
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization HUS Internal Medicine and Rehabilitation
dc.contributor.organization HUS Abdominal Center
dc.contributor.organization Doctoral Programme in Clinical Research
dc.contributor.organization Department of Ophthalmology and Otorhinolaryngology
dc.contributor.organization Silmäklinikka
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Hjelt Institute (-2014)
dc.contributor.organization Department of Public Health
dc.contributor.organization Clinicum
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1553-7390
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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