Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.

Abstract

OBJECTIVE: Crohn's disease (CD) is an intractable inflammatory bowel disease

(IBD) of unknown cause. Recent meta-analysis of the genome-wide association

studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in

Caucasians, however there are limited studies in other populations. METHODS: We

performed a GWAS and two validation studies in the Korean population comprising a

total of 2311 patients with CD and 2442 controls. RESULTS: We confirmed four

previously reported loci: TNFSF15, IL23R, the major histocompatibility complex

region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new

susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43,

combined p=3.60x10(-14)), rs11195128 at 10q25 (OR=1.42, combined p=1.55x10(-10))

and rs11235667 at 11q13 (OR=1.46, combined p=7.15x10(-9)), implicating ATG16L2

and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13

locus revealed a non-synonymous single nucleotide polymorphism (SNP)

(R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with

stronger association (OR=1.61, combined p=2.44x10(-12)) than rs11235667,

suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a

potential causal variant of the association. Two of the three SNPs (rs6856616

(p=0.00024) and rs11195128 (p=5.32x10(-5))) showed consistent patterns of

association in the International IBD Genetics Consortium dataset. Together, the

novel and replicated loci accounted for 5.31% of the total genetic variance for

CD risk in Koreans. CONCLUSIONS: Our study provides new biological insight to CD

and supports the complementary value of genetic studies in different populations.