title: An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians.
abstract: Genome-Wide Association studies (GWAS) of both Crohn's Disease (CD) and Ulcerative Colitis (UC) have unearthed over 40 risk conferring variants. Recently, a meta-analysis on UC revealed several loci, most of which were either previously associated with UC or CD susceptibility in populations of European origin. In this study, we attempted to replicate these findings in an ethnically distinct north Indian UC cohort. 648 UC cases and 850 controls were genotyped using Infinium Human 660W-quad. Out of 59 meta-analysis index SNPs, six were not in the SNP array used in the study. Of the remaining 53 SNPs, four were found monomorphic. Association (p<0.05) at 25 SNPs was observed, of which 15 were CD specific. Only five SNPs namely rs2395185 (HLA-DRA), rs3024505 (IL10), rs6426833 (RNF186), rs3763313 (BTNL2) and rs2066843 (NOD2) retained significance after Bonferroni correction. These results (i) reveal limited replication of Caucasian based meta-analysis results; (ii) reiterate overlapping molecular mechanism(s) in UC and CD; (iii) indicate differences in genetic architecture between populations; and (iv) suggest that resources such as HapMap need to be extended to cover diverse ethnic populations. They also suggest a systematic GWAS in this terrain may be insightful for identifying population specific IBD risk conferring loci and thus enable cross-ethnicity fine mapping of disease loci.
authors.affiliation: Department of Genetics, University of Delhi, South Campus, New Delhi, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Juyal
authors.forename: Pushplata
authors.initials: P
authors.lastname: Prasad
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Senapati
authors.forename: Vandana
authors.initials: V
authors.lastname: Midha
authors.forename: Ajit
authors.initials: A
authors.lastname: Sood
authors.forename: Devendra
authors.initials: D
authors.lastname: Amre
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Juyal
authors.forename: Thelma
authors.initials: T
authors.lastname: BK
mesh_terms: D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005006:Ethnicity; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India; D020641:Polymorphism, Single Nucleotide