Journal article
Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti-dsDNA Autoantibody Production
PLoS genetics, v 7(3), 1001323
01 Mar 2011
PMID: 21408207
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti-dsDNA autoantibody production, a SLE-related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti-dsDNA autoantibody positive (anti-dsDNA +, n = 811) and anti-dsDNA autoantibody negative (anti-dsDNA -, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE. Far fewer and weaker associations were observed for anti-dsDNA - SLE. For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20) compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04), with (Pheterogeneity)<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti-dsDNA + SLE and were not associated with anti-dsDNA - SLE. In conclusion, we identified differential genetic associations with SLE based on anti-dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti-dsDNA - SLE.
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Details
- Title
- Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti-dsDNA Autoantibody Production
- Creators
- Sharon A. Chung - University of California, San FranciscoKimberly E. Taylor - College Station Medical CenterRobert R. Graham - GenentechJoanne Nititham - University of California, San FranciscoAnnette T. Lee - Northwell HealthWard A. Ortmann - GenentechChaim O. Jacob - Southern California University for Professional StudiesMarta E. Alarcon-Riquelme - Oklahoma Medical Research FoundationBetty P. Tsao - University of California, Los AngelesJohn B. Harley - Cincinnati Children's Hospital Medical CenterPatrick M. Gaffney - Oklahoma Medical Research FoundationKathy L. Moser - Oklahoma Medical Research FoundationMichelle Petri - Johns Hopkins UniversityF. Yesim Demirci - University of PittsburghM. Ilyas Kamboh - University of PittsburghSusan Manzi - Allegheny General HospitalPeter K. Gregersen - Northwell HealthCarl D. Langefeld - Wake Forest UniversityTimothy W. Behrens - GenentechLindsey A. Criswell - University of California, San FranciscoSLEGEN
- Publication Details
- PLoS genetics, v 7(3), 1001323
- Publisher
- Public Library Science
- Number of pages
- 11
- Grant note
- M01 RR-000079; M01 RR-000052; M01-RR000056 / U.S. Public Health Service National Center for Research Resources; United States Department of Health & Human Services; United States Public Health Service; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) U54 RR020278 / National Center for Research Resources; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) American College of Rheumatology Mary Kirkland Scholar Awards RR024130; AR043815; AR043814; AR062277; RR020143; AR042460; AI024717; AI063274; AR052125; AR043247; AR043727; AR057028; HL092397; HL088648; HL054900; HL074165; AR002213; AR046588; AR012256; AI095386; AI068759; AR044804; AR02175; AR052300 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000288996600005
- Scopus ID
- 2-s2.0-79953743757
- Other Identifier
- 991021934010804721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity