Journal article
Lupus nephritis susceptibility loci in women with systemic lupus erythematosus
Journal of the American Society of Nephrology, v 25(12), pp 2859-2870
01 Dec 2014
PMID: 24925725
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10(-7)), 16p12 (SLC5A11; P=5.1×10(-7)), 6p22 (ID4; P=7.4×10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1×10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci.
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Details
- Title
- Lupus nephritis susceptibility loci in women with systemic lupus erythematosus
- Creators
- Sharon A Chung - University of California, San FranciscoElizabeth E Brown - University of Alabama at BirminghamAdrienne H Williams - Wake Forest UniversityPaula S Ramos - Medical University of South CarolinaCeline C Berthier - University of MichiganTushar Bhangale - GenentechMarta E Alarcon-Riquelme - Oklahoma Medical Research FoundationTimothy W Behrens - GenentechLindsey A Criswell - University of California, San FranciscoDeborah Cunninghame Graham - King's College LondonF Yesim Demirci - University of PittsburghJeffrey C Edberg - University of Alabama at BirminghamPatrick M Gaffney - Oklahoma Medical Research FoundationJohn B Harley - Oklahoma Medical Research FoundationChaim O Jacob - California Southern UniversityM Ilyas Kamboh - University of PittsburghJennifer A Kelly - Oklahoma Medical Research FoundationSusan Manzi - Temple CollegeKathy L Moser-Sivils - University of OklahomaLaurie P Russell - Wake Forest UniversityMichelle Petri - Johns Hopkins MedicineBetty P Tsao - University of California, Los AngelesTim J Vyse - King's College LondonRaphael Zidovetzki - University of California, RiversideMatthias Kretzler - University of MichiganRobert P Kimberly - University of Alabama at BirminghamBarry I Freedman - Wake Forest UniversityRobert R Graham - GenentechCarl D Langefeld - Wake Forest UniversityInternational Consortium for Systemic Lupus Erythematosus Genetics
- Publication Details
- Journal of the American Society of Nephrology, v 25(12), pp 2859-2870
- Publisher
- American Society of Nephrology (ASN)
- Grant note
- P60-AR053308 / NIAMS NIH HHS AR043247 / NIAMS NIH HHS AR43727 / NIAMS NIH HHS R01 DK079912 / NIDDK NIH HHS R01 AI063274 / NIAID NIH HHS P30-DK081943 / NIDDK NIH HHS R01 AR046588 / NIAMS NIH HHS R01 AR057028 / NIAMS NIH HHS P01 AR049084 / NIAMS NIH HHS 3R37AI024717-23S1 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000345607500020
- Scopus ID
- 2-s2.0-84923869887
- Other Identifier
- 991021934012704721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Urology & Nephrology