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A genome wide association study identifies a lncRna as risk factor for pathological inflammatory responses in leprosy
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نویسنده
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fava v.m. ,manry j. ,cobat a. ,orlova m. ,van thuc n. ,moraes m.o. ,sales-marques c. ,stefani m.m.a. ,latini a.c.p. ,belone a.f. ,thai v.h. ,abel l. ,alcaïs a. ,schurr e.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 2
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چکیده
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Leprosy type-1 reactions (t1rs) are pathological inflammatory responses that afflict a sub-group of leprosy patients and result in peripheral nerve damage. here,we employed a family-based gwas in 221 families with 229 t1r-affect offspring with stepwise replication to identify risk factors for t1r. we discovered,replicated and validated t1r-specific associations with snps located in chromosome region 10p21.2. combined analysis across the three independent samples resulted in strong evidence of association of rs1875147 with t1r (p = 4.5x10-8; or = 1.54,95% ci = 1.32–1.80). the t1r-risk locus was restricted to a lncrna-encoding genomic interval with rs1875147 being an eqtl for the lncrna. since a genetic overlap between leprosy and inflammatory bowel disease (ibd) has been detected,we evaluated if the shared genetic control could be traced to the t1r endophenotype. employing the results of a recent ibd gwas meta-analysis we found that 10.6% of ibd snps available in our dataset shared a common risk-allele with t1r (p = 2.4x10-4). this finding points to a substantial overlap in the genetic control of clinically diverse inflammatory disorders. © 2017 fava et al.
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آدرس
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program in infectious diseases and immunity in global health,research institute of the mcgill university health centre,montreal,qc,canada,the mcgill international tb centre,departments of human genetics and medicine,mcgill university,montreal,qc, Canada, program in infectious diseases and immunity in global health,research institute of the mcgill university health centre,montreal,qc,canada,the mcgill international tb centre,departments of human genetics and medicine,mcgill university,montreal,qc, Canada, laboratory of human genetics of infectious diseases,necker branch,institut national de la santé et de la recherche médicale u.1163,paris,france,university paris descartes,imagine institute,paris,france,giles laboratory of human genetics of infectious diseases,rockefeller branch,rockefeller university,new york, United States, program in infectious diseases and immunity in global health,research institute of the mcgill university health centre,montreal,qc,canada,the mcgill international tb centre,departments of human genetics and medicine,mcgill university,montreal,qc, Canada, hospital for dermato-venerology,ho chi minh city, Viet Nam, laboratório de hanseníase,instituto oswaldo cruz,fiocruz,rio de janeiro, Brazil, laboratório de hanseníase,instituto oswaldo cruz,fiocruz,rio de janeiro, Brazil, tropical pathology and public health institute,federal university of goiás,goiânia, Brazil, lauro de souza lima institute,bauru, Brazil, lauro de souza lima institute,bauru, Brazil, hospital for dermato-venerology,ho chi minh city, Viet Nam, laboratory of human genetics of infectious diseases,necker branch,institut national de la santé et de la recherche médicale u.1163,paris,france,university paris descartes,imagine institute,paris,france,giles laboratory of human genetics of infectious diseases,rockefeller branch,rockefeller university,new york, United States, laboratory of human genetics of infectious diseases,necker branch,institut national de la santé et de la recherche médicale u.1163,paris,france,university paris descartes,imagine institute,paris,france,giles laboratory of human genetics of infectious diseases,rockefeller branch,rockefeller university,new york, United States, program in infectious diseases and immunity in global health,research institute of the mcgill university health centre,montreal,qc,canada,the mcgill international tb centre,departments of human genetics and medicine,mcgill university,montreal,qc, Canada
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Authors
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