Genome-Wide Association Study of Ulcerative Colitis in Koreans Suggests Extensive Overlapping of Genetic Susceptibility With Caucasians

Yang, Suk Kyun; Hong, Myunghee; Zhao, Wanting; Jung, Yoojin; Tayebi, Naeimeh; Ye, Byong Duk; Kim, Kyung Jo; Park, Sang Hyoung; Lee, Inchul; Shin, Hyoung Doo; Cheong, Hyun Sub; Kim, Lyoung Hyo; Kim, Hyo Jong; Jung, Sung Ae; Kang, Daehee; Youn, Hee Shang; Li, Jianjun; Song, Kyuyoung

doi:10.1097/mib.0b013e3182802ab6

Cited by 71 publications

(45 citation statements)

References 41 publications

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“…10 The non-European UC GWAS performed to date also identified novel susceptibility loci 11 and revealed shared UC risk loci between European and non-European cohorts. 12 These UC-specific studies also confirmed the longestablished association between UC and the classical human leukocyte antigen (HLA) locus, which contains genes encoding antigenpresenting proteins, and plays a crucial role in the regulation of the adaptive immune system.…”

Section: Introductionmentioning

confidence: 54%

“…13 However, neither CFB nor SLC44A4 have been identified in any of the larger Caucasian GWAS, [3][4][5][6][7] their meta-analysis 8,9 and more recently in ImmunoChip analysis, 10 or in the non-European UC cohorts studied to date. 11,12 Needless to say, such a striking difference across ethnic groups may be due to inherent statistical limitations of GWAS, which mainly relies on single SNP analysis, incomplete coverage of functional common or rare variants, poor representation of appropriate proxies on commercial genotyping arrays due to population-specific LD patterns, among others factors like allelic/genetic heterogeneity, varying environmental components like gut microbiome influenced by geographical location, lifestyle factors such as diet, smoking, etc. leaving much of the disease heritability unexplained.…”

Section: In Silico Analysis Of Slc44a4 Snpsmentioning

confidence: 99%

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A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility

et al. 2016

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The first ever genome-wide association study (GWAS) of ulcerative colitis in genetically distinct north Indian population identified two novel genes namely CFB and SLC44A4. Considering their biological relevance, we investigated allelic/genetic heterogeneity in these genes among ulcerative colitis cohorts of north Indian, Japanese and Dutch origin using high-density ImmunoChip casecontrol genotype data. Comparative linkage disequilibrium profiling and test of association were performed. Of the 28 CFB SNPs, similar strength of association was observed for rs4151657 (novel ulcerative colitis GWAS SNP) in north Indians (P = 1.73 × 10 − 10 ) and Japanese (P = 2.02 × 10 − 12 ) but not in the Dutch. Further, a three-marker haplotype was shared between north Indians and Japanese (Po10 − 8 ), but a different five-marker haplotype was associated (P = 2.07 × 10 − 6 ) in the Dutch. Of the 22 SLC44A4 SNPs, rs2736428 (novel ulcerative colitis GWAS SNP) was found significantly associated in north Indians (P = 4.94 × 10 − 10 ) and Japanese (P = 3.37 × 10 − 9 ), but not among the Dutch. These results suggest (i) apparent allelic heterogeneity in CFB and genetic heterogeneity in SLC44A4 across different ethnic groups; (ii) shared ulcerative colitis genetic etiological factors among Asians; and finally (iii) re-exploration of GWAS findings together with high-density genotyping/ sequencing and trans-ethnic fine mapping approaches may help identify shared and population-specific risk variants and enable to explain missing disease heritability.

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Section: Introductionmentioning

confidence: 54%

Section: In Silico Analysis Of Slc44a4 Snpsmentioning

confidence: 99%

A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility

et al. 2016

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“…Meta-analysis of the GWAS identified 163 risk loci for IBD [4]. GWAS of IBD in Asia have been reported in Japan, Korea and India [24,25,26,27,28,29,30]. The loci identified in Asian studies are listed in table 2.…”

Section: Ibd Genetic Studies In Asiamentioning

confidence: 99%

Risk Genes of Inflammatory Bowel Disease in Asia: What Are the Most Important Pathways Affected?

Guo

Wu²

2016

Dig Dis

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Genetic factors play an important role in the pathogenesis of inflammatory bowel disease (IBD), and IBD is now recognized as a complex disease that results from interplay between genetic and environment factors. To date, over 160 IBD-susceptible loci have been identified using genome-wide association studies (GWAS). The risk genes identified in these studies are involved in various pathways in innate and adaptive immune response such as innate bacterial sensing, autophagy and interleukin-23 receptor/T-helper cell 17 pathway. It was initially believed that the genetic backgrounds of Asian IBD patients differ from that of other populations. Recent GWAS and meta-analysis found that there is pervasive sharing of risk loci between the East and West. Overlapping risk genes between populations of different ancestries indicate that pathways underlying the etiology of IBD may be common between Asia and other areas. However, the importance of individual pathways may be different in Asia from the Western countries. Identifying the most important pathways affected in Asian IBD patients may provide a better understanding of pathogenesis of IBD in Asia and improve the clinical management of the patients.

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“…We combined data from 915 individuals with IBD [CD, 532; UC, 383] and 745 healthy controls included in our previously published GWAS, 29,31 with additional data of 590 individuals with IBD [CD, 390; UC, 200] and 3296 population controls from the Korea National Institute of Health, to increase the power of our GWAS-based discovery analysis. 27 The …”

Section: Study Populationmentioning

confidence: 99%

“…In our previously published GWAS, 29,31 IBD cases were genotyped using Illumina OmniExpress arrays; newly included IBD cases were genotyped using Illumina OmniExpressExome arrays. 27 All controls were genotyped using Illumina Omni1-Quad arrays.…”

Section: Genotyping and Quality Controlmentioning

confidence: 99%

X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans

Lee

Yang

et al. 2017

Journal of Crohn's and Colitis

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Background and Aims: Genome-wide association studies of inflammatory bowel disease identified > 200 susceptibility loci only in autosomes. This study aimed to identify inflammatory bowel disease susceptibility loci on the X chromosome. Methods: We performed an X chromosome-wide association study in Korean patients with inflammatory bowel disease. We analysed X chromosome data from our recent genome-wide association studies, including 1505 cases [922 Crohn's disease and 583 ulcerative colitis] and 4041 controls during the discovery phase, followed by replication in additional 1989 cases [993 Crohn's disease, 996 ulcerative colitis] and 3491 controls. Sex-related differential effects of single nucleotide polymorphisms on disease were also evaluated. Results: We confirmed a significant association of a previously reported inflammatory bowel disease susceptibility locus at chromosome Xq26.3 [CD40LG-ARHGEF6; odds ratio, 1.22; 95% confidence interval, 1.16-1.28; combined p = 3.79 × 10]. This locus accounted for 0.18% and 0.12% of genetic variance in Crohn's disease and ulcerative colitis, respectively, and increased the total autosomal chromosome genetic variance from 6.65% to 6.83% and from 5.47% to 5.59% for Crohn's disease and ulcerative colitis risk, respectively, in the Korean population. Sex-stratified analyses did not reveal sex-related differences in effect sizes. Conclusions:We confirmed the association of rs2427870 at the CD40LG-ARHGEF6 locus with an inflammatory bowel disease through an X chromosome-wide association study in a Korean Downloaded from https://academic.oup.com/ecco-jcc/article-abstract/11/7/820/3041097 by guest on 07 June 2019 population. Our data suggest that the CD40LG-ARHGEF6 locus on the X chromosome might play a role in inflammatory bowel disease pathogenesis in the Korean population.

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Genome-Wide Association Study of Ulcerative Colitis in Koreans Suggests Extensive Overlapping of Genetic Susceptibility With Caucasians

Cited by 71 publications

References 41 publications

A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility

A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility

Risk Genes of Inflammatory Bowel Disease in Asia: What Are the Most Important Pathways Affected?

X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans

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