An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in North Indians

Garima Juyal, Pushplata Prasad, Sabyasachi Senapati, Vandana Midha, Ajit Sood, Devendra Amre, Ramesh C. Juyal, B. K. Thelma

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere16565
JournalPLoS One
Volume6
Issue number1
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

colitis
Ulcerative Colitis
Crohn disease
Genes
Single Nucleotide Polymorphism
Genome
Crohn Disease
loci
genome
meta-analysis
Meta-Analysis
Genome-Wide Association Study
HLA-DR alpha-Chains
Population
HapMap Project
Interleukin-10
Disease Susceptibility
nationalities and ethnic groups
disease resistance

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in North Indians. / Juyal, Garima; Prasad, Pushplata; Senapati, Sabyasachi; Midha, Vandana; Sood, Ajit; Amre, Devendra; Juyal, Ramesh C.; Thelma, B. K.

In: PLoS One, Vol. 6, No. 1, e16565, 2011.

Research output: Contribution to journalArticle

Juyal, Garima ; Prasad, Pushplata ; Senapati, Sabyasachi ; Midha, Vandana ; Sood, Ajit ; Amre, Devendra ; Juyal, Ramesh C. ; Thelma, B. K. / An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in North Indians. In: PLoS One. 2011 ; Vol. 6, No. 1.
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