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

Aditi Gupta, Garima Juyal, Ajit Sood, Vandana Midha, Keiko Yamazaki, Arnau Vich Vila, Motohiro Esaki, Toshiyuki Matsui, Atsushi Takahashi, Michiaki Kubo, Rinse K. Weersma, B. K. Thelma

Research output: Contribution to journalArticle

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Abstract

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 case-control 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 (P<10 -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.

Original languageEnglish
Pages (from-to)111-112
Number of pages2
JournalEuropean Journal of Human Genetics
Volume25
Issue number1
DOIs
Publication statusPublished - 01-01-2016

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Genome-Wide Association Study
Disease Susceptibility
Ulcerative Colitis
Single Nucleotide Polymorphism
Genetic Heterogeneity
Haplotypes
Linkage Disequilibrium
Ethnic Groups
Population
Genes
Genotype
Surveys and Questionnaires

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Gupta, Aditi ; Juyal, Garima ; Sood, Ajit ; Midha, Vandana ; Yamazaki, Keiko ; Vich Vila, Arnau ; Esaki, Motohiro ; Matsui, Toshiyuki ; Takahashi, Atsushi ; Kubo, Michiaki ; Weersma, Rinse K. ; Thelma, B. K. / A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility. In: European Journal of Human Genetics. 2016 ; Vol. 25, No. 1. pp. 111-112.
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abstract = "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 case-control 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 (P<10 -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.",
author = "Aditi Gupta and Garima Juyal and Ajit Sood and Vandana Midha and Keiko Yamazaki and {Vich Vila}, Arnau and Motohiro Esaki and Toshiyuki Matsui and Atsushi Takahashi and Michiaki Kubo and Weersma, {Rinse K.} and Thelma, {B. K.}",
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Gupta, A, Juyal, G, Sood, A, Midha, V, Yamazaki, K, Vich Vila, A, Esaki, M, Matsui, T, Takahashi, A, Kubo, M, Weersma, RK & Thelma, BK 2016, 'A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility', European Journal of Human Genetics, vol. 25, no. 1, pp. 111-112. https://doi.org/10.1038/ejhg.2016.131

A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility. / Gupta, Aditi; Juyal, Garima; Sood, Ajit; Midha, Vandana; Yamazaki, Keiko; Vich Vila, Arnau; Esaki, Motohiro; Matsui, Toshiyuki; Takahashi, Atsushi; Kubo, Michiaki; Weersma, Rinse K.; Thelma, B. K.

In: European Journal of Human Genetics, Vol. 25, No. 1, 01.01.2016, p. 111-112.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility

AU - Gupta, Aditi

AU - Juyal, Garima

AU - Sood, Ajit

AU - Midha, Vandana

AU - Yamazaki, Keiko

AU - Vich Vila, Arnau

AU - Esaki, Motohiro

AU - Matsui, Toshiyuki

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Weersma, Rinse K.

AU - Thelma, B. K.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 case-control 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 (P<10 -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.

AB - 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 case-control 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 (P<10 -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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