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Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci
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نویسنده
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zhernakova a. ,stahl e.a. ,trynka g. ,raychaudhuri s. ,festen e.a. ,franke l. ,westra h.-j. ,fehrmann r.s.n. ,kurreeman f.a.s. ,thomson b. ,gupta n. ,romanos j. ,mcmanus r. ,ryan a.w. ,turner g. ,brouwer e. ,posthumus m.d. ,remmers e.f. ,tucci f. ,toes r. ,grandone e. ,mazzilli m.c. ,rybak a. ,cukrowska b. ,coenen m.j.h. ,radstake t.r.d.j. ,van riel p.l.c.m. ,li y. ,de bakker p.i.w. ,gregersen p.k. ,worthington j. ,siminovitch k.a. ,klareskog l. ,huizinga t.w.j. ,wijmenga c. ,plenge r.m.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 2
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چکیده
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Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (cd) and rheumatoid arthritis (ra),but the extent of this sharing has not been systematically explored. previous studies demonstrate that 6 of the established non-hla cd and ra risk loci (out of 26 loci for each disease) are shared between both diseases. we hypothesized that there are additional shared risk alleles and that combining genome-wide association study (gwas) data from each disease would increase power to identify these shared risk alleles. we performed a meta-analysis of two published gwas on cd (4,533 cases and 10,750 controls) and ra (5,539 cases and 17,231 controls). after genotyping the top associated snps in 2,169 cd cases and 2,255 controls,and 2,845 ra cases and 4,944 controls,8 additional snps demonstrated p<5×10-8 in a combined analysis of all 50,266 samples,including four snps that have not been previously confirmed in either disease: rs10892279 near the ddx6 gene (pcombined = 1.2×10-12),rs864537 near cd247 (pcombined = 2.2×10-11),rs2298428 near ube2l3 (pcombined = 2.5×10-10),and rs11203203 near ubash3a (pcombined = 1.1×10-8). we also confirmed that 4 gene loci previously established in either cd or ra are associated with the other autoimmune disease at combined p<5×10-8 (sh2b3,8q24,stat4,and traf1-c5). from the 14 shared gene loci,7 snps showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (ld) block around the snp. these associations implicate antigen presentation and t-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.
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آدرس
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department of rheumatology,leiden university medical center,leiden,netherlands,complex genetics section,department of medical genetics,university medical centre utrecht,utrecht,netherlands,division of rheumatology,immunology,and allergy,brigham and women's hospital,boston,ma, United States, division of rheumatology,immunology,and allergy,brigham and women's hospital,boston,ma,united states,broad institute,cambridge,ma, United States, genetics department,university medical centre groningen and university of groningen,groningen, Netherlands, division of rheumatology,immunology,and allergy,brigham and women's hospital,boston,ma,united states,broad institute,cambridge,ma,united states,center for human genetic research,massachusetts general hospital,boston,ma,united states,division of genetics,brigham and women's hospital,boston,ma, United States, genetics department,university medical centre groningen and university of groningen,groningen, Netherlands, genetics department,university medical centre groningen and university of groningen,groningen,netherlands,blizard institute of cell and molecular science,barts and the london school of medicine and dentistry,queen mary university of london,london, United Kingdom, genetics department,university medical centre groningen and university of groningen,groningen, Netherlands, genetics department,university medical centre groningen and university of groningen,groningen, Netherlands, department of rheumatology,leiden university medical center,leiden,netherlands,division of rheumatology,immunology,and allergy,brigham and women's hospital,boston,ma,united states,broad institute,cambridge,ma, United States, broad institute,cambridge,ma, United States, broad institute,cambridge,ma, United States, genetics department,university medical centre groningen and university of groningen,groningen, Netherlands, department of clinical medicine and institute of molecular medicine,trinity centre for health sciences,trinity college,st james's hospital,dublin, Ireland, department of clinical medicine and institute of molecular medicine,trinity centre for health sciences,trinity college,st james's hospital,dublin, Ireland, department of clinical medicine and institute of molecular medicine,trinity centre for health sciences,trinity college,st james's hospital,dublin, Ireland, department of rheumatology and clinical immunology,university medical center groningen and university of groningen,groningen, Netherlands, department of rheumatology and clinical immunology,university medical center groningen and university of groningen,groningen, Netherlands, genetics and genomics branch,national institute of arthritis and musculoskeletal and skin diseases,national institutes of health,bethesda,md, United States, european laboratory for food induced disease,university of naples federico ii,naples, Italy, department of rheumatology,leiden university medical center,leiden, Netherlands, unita' di aterosclerosi e trombosi,i.r.c.c.s casa sollievo della sofferenza,s. giovanni rotondo,foggia, Italy, department of experimental medicine,sapienza university of rome,rome, Italy, department of gastroenterology,hepatology,and immunology,children's memorial health institute,warsaw, Poland, department of pathology,children's memorial health institute,warsaw, Poland, department of human genetics,radboud university nijmegen medical centre,nijmegen, Netherlands, department of rheumatology,radboud university nijmegen medical centre,nijmegen, Netherlands, department of rheumatology,radboud university nijmegen medical centre,nijmegen, Netherlands, celera,alameda,ca, United States, division of rheumatology,immunology,and allergy,brigham and women's hospital,boston,ma,united states,broad institute,cambridge,ma,united states,division of genetics,department of medicine,brigham and women's hospital,harvard medical school,boston,ma,united states,julius center for health sciences and primary care,university medical center utrecht, Netherlands, the feinstein institute for medical research,north shore-long island jewish health system,manhasset,ny, United States, arthritis research campaign-epidemiology unit,the university of manchester,manchester, United Kingdom, department of medicine,university of toronto,mount sinai hospital and university health network,toronto, Canada, rheumatology unit,department of medicine,karolinska institutet at karolinska university hospital solna,stockholm, Sweden, department of rheumatology,leiden university medical center,leiden, Netherlands, genetics department,university medical centre groningen and university of groningen,groningen, Netherlands, division of rheumatology,immunology,and allergy,brigham and women's hospital,boston,ma,united states,broad institute,cambridge,ma,united states,division of genetics,brigham and women's hospital,boston,ma, United States
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Authors
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