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A genome-wide scan of ashkenazi jewish crohn's disease suggests novel susceptibility loci
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نویسنده
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kenny e.e. ,pe'er i. ,karban a. ,ozelius l. ,mitchell a.a. ,ng s.m. ,erazo m. ,ostrer h. ,abraham c. ,abreu m.t. ,atzmon g. ,barzilai n. ,brant s.r. ,bressman s. ,burns e.r. ,chowers y. ,clark l.n. ,darvasi a. ,doheny d. ,duerr r.h. ,eliakim r. ,giladi n. ,gregersen p.k. ,hakonarson h. ,jones m.r. ,marder k. ,mcgovern d.p.b. ,mulle j. ,orr-urtreger a. ,proctor d.d. ,pulver a. ,rotter j.i. ,silverberg m.s. ,ullman t. ,warren s.t. ,waterman m. ,zhang w. ,bergman a. ,mayer l. ,katz s. ,desnick r.j. ,cho j.h. ,peter i.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 3
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چکیده
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Crohn's disease (cd) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. the largest meta-analysis of genome-wide association to date identified 71 cd-susceptibility loci in individuals of european ancestry. an important epidemiological feature of cd is that it is 2-4 times more prevalent among individuals of ashkenazi jewish (aj) descent compared to non-jewish europeans (nj). to explore genetic variation associated with cd in ajs,we conducted a genome-wide association study (gwas) by combining raw genotype data across 10 aj cohorts consisting of 907 cases and 2,345 controls in the discovery stage,followed up by a replication study in 971 cases and 2,124 controls. we confirmed genome-wide significant associations of 9 known cd loci in ajs and replicated 3 additional loci with strong signal (p<5×10 -6). novel signals detected among ajs were mapped to chromosomes 5q21.1 (rs7705924,combined p = 2×10 -8; combined odds ratio or = 1.48),2p15 (rs6545946,p = 7×10 -9; or = 1.16),8q21.11 (rs12677663,p = 2×10 -8; or = 1.15),10q26.3 (rs10734105,p = 3×10 -8; or = 1.27),and 11q12.1 (rs11229030,p = 8×10 -9; or = 1.15),implicating biologically plausible candidate genes,including rpl7,cpamd8,prg2,and prg3. in all,the 16 replicated and newly discovered loci,in addition to the three coding nod2 variants,accounted for 11.2% of the total genetic variance for cd risk in the aj population. this study demonstrates the complementary value of genetic studies in the ashkenazim. © 2012 kenny et al.
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آدرس
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department of computer sciences,columbia university,new york,ny,united states,department of genetics,stanford university school of medicine,stanford,ca, United States, department of computer sciences,columbia university,new york,ny, United States, department of gastroenterology,rambam health care campus,b. rappaport institute for research in the medical sciences,faculty of medicine,technion-israel institute of technology,haifa, Israel, department of genetics and genomic sciences,mount sinai school of medicine,new york,ny, United States, department of genetics and genomic sciences,mount sinai school of medicine,new york,ny, United States, department of medicine,section of digestive diseases,yale university,new haven,ct, United States, department of genetics and genomic sciences,mount sinai school of medicine,new york,ny, United States, department of pathology,albert einstein college of medicine,new york,ny, United States, department of medicine,section of digestive diseases,yale university,new haven,ct, United States, division of gastroenterology,university of miami miller school of medicine,miami,fl, United States, genetic core for longevity,institute for aging research and the diabetes research center,albert einstein college of medicine,bronx,ny, United States, genetic core for longevity,institute for aging research and the diabetes research center,albert einstein college of medicine,bronx,ny, United States, meyerhoff inflammatory bowel disease center,department of medicine,johns hopkins university school of medicine,baltimore,md,united states,department of epidemiology,bloomberg school of public health,johns hopkins university,baltimore,md, United States, mirken department of neurology,beth israel medical center,new york,ny,united states,the saul r. korey department of neurology,albert einstein college of medicine,bronx,ny, United States, department of medicine,albert einstein college of medicine,bronx,ny, United States, department of gastroenterology,rambam health care campus,b. rappaport institute for research in the medical sciences,faculty of medicine,technion-israel institute of technology,haifa, Israel, department of pathology and cell biology,columbia university,new york,ny, United States, the institute of life sciences,hebrew university of jerusalem,jerusalem, Israel, department of genetics and genomic sciences,mount sinai school of medicine,new york,ny, United States, division of gastroenterology,hepatology,and nutrition,department of medicine,university of pittsburgh school of medicine,pittsburgh,pa,united states,department of human genetics,graduate school of public health,university of pittsburgh,pittsburgh,pa, United States, department of gastroenterology and hepatology,sheba medical center,raman gan, Israel, department of neurology,tel aviv sourasky medical center,sackler school of medicine,tel aviv university,tel-aviv, Israel, robert s. boas center for genomics and human genetics,feinstein institute for medical research,north shore lij health system,manhasset,ny, United States, center for applied genomics,the children's hospital of philadelphia,university of pennsylvania school of medicine,philadelphia,pa, United States, division of endocrinology,diabetes,and metabolism,graduate program in biomedical sciences and translational medicine,cedars-sinai medical center,los angeles,ca, United States, department of neurology,college of physicians and surgeons,columbia university,new york,ny,united states,taub institute for research on alzheimer's disease and the aging brain,college of physicians and surgeons,columbia university,new york,ny, United States, department of translational medicine,inflammatory bowel and immunobiology research institute,cedars-sinai medical center,los angeles,ca,united states,medical genetics institute,cedars-sinai medical center,los angeles,ca, United States, department of human genetics,emory university school of medicine,atlanta,ga, United States, genetic institute,tel aviv sourasky medical center,sackler school of medicine,tel aviv university,tel-aviv, Israel, department of medicine,section of digestive diseases,yale university,new haven,ct, United States, epidemiology-genetics program in schizophrenia,bipolar disorders,and related disorders,department of psychiatry and behavioral sciences,school of medicine,johns hopkins university,baltimore,md,united states,department of epidemiology,bloomberg school of public health,johns hopkins university,baltimore,md, United States, medical genetics institute,cedars-sinai medical center,los angeles,ca, United States, ibd group,mount sinai hospital,university of toronto,toronto, Canada, division of gastroenterology,department of medicine,mount sinai school of medicine,new york,ny, United States, department of human genetics,emory university school of medicine,atlanta,ga,united states,departments of biochemistry and pediatrics,emory university school of medicine,atlanta,ga, United States, department of gastroenterology,rambam health care campus,b. rappaport institute for research in the medical sciences,faculty of medicine,technion-israel institute of technology,haifa, Israel, department of medicine,section of digestive diseases,yale university,new haven,ct, United States, department of systems and computational biology,albert einstein college of medicine,new york,ny, United States, division of gastroenterology,department of medicine,mount sinai school of medicine,new york,ny, United States, albert einstein college of medicine,north shore university hospital-long island jewish hospital systems,st. francis hospital,great neck,ny, United States, department of genetics and genomic sciences,mount sinai school of medicine,new york,ny, United States, department of medicine,section of digestive diseases,yale university,new haven,ct, United States, department of genetics and genomic sciences,mount sinai school of medicine,new york,ny, United States
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Authors
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