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A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap
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نویسنده
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ramos p.s. ,criswell l.a. ,moser k.l. ,comeau m.e. ,williams a.h. ,pajewski n.m. ,chung s.a. ,graham r.r. ,zidovetzki r. ,kelly j.a. ,kaufman k.m. ,jacob c.o. ,vyse t.j. ,tsao b.p. ,kimberly r.p. ,gaffney p.m. ,alarcón-riquelme m.e. ,harley j.b. ,langefeld c.d.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 12
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چکیده
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In spite of the well-known clustering of multiple autoimmune disorders in families,analyses of specific shared genes and polymorphisms between systemic lupus erythematosus (sle) and other autoimmune diseases (ads) have been limited. therefore,we comprehensively tested autoimmune variants for association with sle,aiming to identify pleiotropic genetic associations between these diseases. we compiled a list of 446 non-major histocompatibility complex (mhc) variants identified in genome-wide association studies (gwas) of populations of european ancestry across 17 ads. we then tested these variants in our combined caucasian sle cohorts of 1,500 cases and 5,706 controls. we tested a subset of these polymorphisms in an independent caucasian replication cohort of 2,085 sle cases and 2,854 controls,allowing the computation of a meta-analysis between all cohorts. we have uncovered novel shared sle loci that passed multiple comparisons adjustment,including the vtcn1 (rs12046117,p = 2.02×10 -06) region. we observed that the loci shared among the most ads include il23r,olig3/tnfaip3,and il2ra. given the lack of a universal autoimmune risk locus outside of the mhc and variable specificities for different diseases,our data suggests partial pleiotropy among ads. hierarchical clustering of ads suggested that the most genetically related ads appear to be type 1 diabetes with rheumatoid arthritis and crohn's disease with ulcerative colitis. these findings support a relatively distinct genetic susceptibility for sle. for many of the shared gwas autoimmune loci,we found no evidence for association with sle,including il23r. also,several established sle loci are apparently not associated with other ads,including the itgam-itgax and tnfsf4 regions. this study represents the most comprehensive evaluation of shared autoimmune loci to date,supports a relatively distinct non-mhc genetic susceptibility for sle,provides further evidence for previously and newly identified shared genes in sle,and highlights the value of studies of potentially pleiotropic genes in autoimmune diseases. © 2011 ramos et al.
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آدرس
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department of medicine,medical university of south carolina,charleston,sc, United States, rosalind russell medical research center for arthritis,university of california san francisco,san francisco,ca, United States, arthritis and immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, department of biostatistical sciences,wake forest university health sciences,winston-salem,nc, United States, department of biostatistical sciences,wake forest university health sciences,winston-salem,nc, United States, department of biostatistical sciences,wake forest university health sciences,winston-salem,nc, United States, rosalind russell medical research center for arthritis,university of california san francisco,san francisco,ca, United States, immunology biomarkers group,genentech,south san francisco,ca, United States, department of cell biology and neuroscience,university of california riverside,riverside,ca, United States, arthritis and immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, division of rheumatology,cincinnati children's hospital medical center,cincinnati,oh, United States, department of medicine,keck school of medicine,university of southern california,los angeles,ca, United States, division of genetics and molecular medicine,king's college london,london, United Kingdom, david geffen school of medicine,university of california los angeles,los angeles,ca, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, arthritis and immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, arthritis and immunology research program,oklahoma medical research foundation,oklahoma city,ok,united states,centro de genómica y investigaciones oncológicas,pfizer-universidad de granada-junta de andalucía,granada, Spain, division of rheumatology,cincinnati children's hospital medical center,cincinnati,oh, United States, department of biostatistical sciences,wake forest university health sciences,winston-salem,nc, United States
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Authors
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