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A meta-analysis of genome-wide association scans identifies IL18RAP,PTPN2,TAGAP,and PUS10 as shared risk loci for crohn's disease and celiac disease
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نویسنده
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festen e.a.m. ,goyette p. ,green t. ,boucher g. ,beauchamp c. ,trynka g. ,dubois p.c. ,lagacé c. ,stokkers p.c.f. ,hommes d.w. ,barisani d. ,palmieri o. ,annese v. ,van heel d.a. ,weersma r.k. ,daly m.j. ,wijmenga c. ,rioux j.d.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 1
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چکیده
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Crohn's disease (cd) and celiac disease (celd) are chronic intestinal inflammatory diseases,involving genetic and environmental factors in their pathogenesis. the two diseases can co-occur within families,and studies suggest that celd patients have a higher risk to develop cd than the general population. these observations suggest that cd and celd may share common genetic risk loci. two such shared loci,il18rap and ptpn2,have already been identified independently in these two diseases. the aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (gwas) datasets of cd and celd. specifically,gwas results from celd (768 cases,1,422 controls) and cd (3,230 cases,4,829 controls) were combined in a meta-analysis. nine independent regions had nominal association p-value <1.0×10-5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1×10-2 in celd and <1×10-3in cd). these include the two previously reported shared loci,il18rap and ptpn2,with p-values of 3.37×10-8 and 6.39×10-9,respectively,in the meta-analysis. the other seven had not been reported as shared loci and thus were tested in additional celd (3,149 cases and 4,714 controls) and cd (1,835 cases and 1,669 controls) cohorts. two of these loci,tagap and pus10,showed significant evidence of replication (bonferroni corrected p-values <0.0071) in the combined celd and cd replication cohorts and were firmly established as shared risk loci of genome-wide significance,with overall combined p-values of 1.55×10-10 and 1.38×10-11 respectively. through a meta-analysis of gwas data from cd and celd,we have identified four shared risk loci: ptpn2,il18rap,tagap,and pus10. the combined analysis of the two datasets provided the power,lacking in the individual gwas for single diseases,to detect shared loci with a relatively small effect. © 2011 festen et al.
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آدرس
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department of gastroenterology and hepatology,university medical centre groningen,university of groningen,groningen,netherlands,department of genetics,university medical centre groningen and university of groningen,groningen, Netherlands, research center,université de montréal and the montreal heart institute,montreal,qc, Canada, the broad institute,cambridge,ma, United States, research center,université de montréal and the montreal heart institute,montreal,qc, Canada, research center,université de montréal and the montreal heart institute,montreal,qc, Canada, department of genetics,university medical centre groningen and university of groningen,groningen, Netherlands, centre for digestive diseases,blizard institute of cell and molecular science,barts and the london school of medicine and dentistry,queen mary university of london,london, United Kingdom, research center,université de montréal and the montreal heart institute,montreal,qc, Canada, department of gastroenterology and hepatology,academic medical centre,amsterdam, Netherlands, department of gastroenterology and hepatology,leiden university medical centre,leiden, Netherlands, department of experimental medicine,faculty of medicine,university of milano-bicocca,monza, Italy, u. o. gastroenterologia ed endoscopia digestiva,ospedale casa sollievo della sofferenza,irccs,san giovanni rotondo, Italy, u. o. gastroenterologia ed endoscopia digestiva,ospedale casa sollievo della sofferenza,irccs,san giovanni rotondo, Italy, centre for digestive diseases,blizard institute of cell and molecular science,barts and the london school of medicine and dentistry,queen mary university of london,london, United Kingdom, department of gastroenterology and hepatology,university medical centre groningen,university of groningen,groningen, Netherlands, the broad institute,cambridge,ma,united states,center for human genetic research,massachusetts general hospital,harvard medical school,boston,ma, United States, department of genetics,university medical centre groningen and university of groningen,groningen, Netherlands, research center,université de montréal and the montreal heart institute,montreal,qc, Canada
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Authors
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