Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn's disease and ulcerative colitis

Junji Umeno, Kouichi Asano, Tomonaga Matsushita, Takayuki Matsumoto, Yutaka Kiyohara, Mitsuo Iida, Yusuke Nakamura, Naoyuki Kamatani, Michiaki Kubo

Research output: Contribution to journalArticle

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Abstract

Background: Both ulcerative colitis (UC) and Crohn's disease (CD) have a complex etiology involving multiple genetic and environmental factors. Many genome-wide association studies (GWAS) and subsequent replication studies revealed that both diseases share some of the susceptibility loci; however, common genetic factors for both diseases are not fully elucidated. This study is aimed to identify the common genetic factors for CD and UC by a meta-analysis of published studies. Methods: We first reviewed the 10 GWAS for CD to select candidate single nucleotide polymorphisms (SNPs). Next, we performed a PubMed literature search up to June 30, 2010 and carried out a systemic review of published studies that examined the association of CD susceptibility loci in UC patients. Meta-analysis was carried out using the inverse variance-weighted method or the DerSimonian-Laird method after estimating the heterogeneity among the studies. The data for highly linked SNPs were combined. Finally, we performed a meta-analysis of 43 published studies in 45 SNPs located at 33 loci by using a total of 4852 to 31,125 subjects. Results: We confirmed the association of 17 reported common susceptibility loci. Moreover, we found associations at eight additional loci: GCKR, ATG16L1, CDKAL1, ZNF365, LRRK2-MUC19, C13orf31, PTPN2, and SBNO2. The genetic risk of each locus was modest (odds ratios ranged from 1.05-1.22) except IL23R. Conclusions: These results indicate that CD and UC share many susceptibility loci with small genetic effect. Our data provide further understanding of the common pathogenesis between CD and UC.

Original languageEnglish
Pages (from-to)2407-2415
Number of pages9
JournalInflammatory Bowel Diseases
Volume17
Issue number12
DOIs
Publication statusPublished - 01-12-2011
Externally publishedYes

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Ulcerative Colitis
Crohn Disease
Meta-Analysis
Single Nucleotide Polymorphism
Genome-Wide Association Study
Disease Susceptibility
PubMed
Odds Ratio

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Umeno, Junji ; Asano, Kouichi ; Matsushita, Tomonaga ; Matsumoto, Takayuki ; Kiyohara, Yutaka ; Iida, Mitsuo ; Nakamura, Yusuke ; Kamatani, Naoyuki ; Kubo, Michiaki. / Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn's disease and ulcerative colitis. In: Inflammatory Bowel Diseases. 2011 ; Vol. 17, No. 12. pp. 2407-2415.
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Umeno, J, Asano, K, Matsushita, T, Matsumoto, T, Kiyohara, Y, Iida, M, Nakamura, Y, Kamatani, N & Kubo, M 2011, 'Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn's disease and ulcerative colitis', Inflammatory Bowel Diseases, vol. 17, no. 12, pp. 2407-2415. https://doi.org/10.1002/ibd.21651

Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn's disease and ulcerative colitis. / Umeno, Junji; Asano, Kouichi; Matsushita, Tomonaga; Matsumoto, Takayuki; Kiyohara, Yutaka; Iida, Mitsuo; Nakamura, Yusuke; Kamatani, Naoyuki; Kubo, Michiaki.

In: Inflammatory Bowel Diseases, Vol. 17, No. 12, 01.12.2011, p. 2407-2415.

Research output: Contribution to journalArticle

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T1 - Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn's disease and ulcerative colitis

AU - Umeno, Junji

AU - Asano, Kouichi

AU - Matsushita, Tomonaga

AU - Matsumoto, Takayuki

AU - Kiyohara, Yutaka

AU - Iida, Mitsuo

AU - Nakamura, Yusuke

AU - Kamatani, Naoyuki

AU - Kubo, Michiaki

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Y1 - 2011/12/1

N2 - Background: Both ulcerative colitis (UC) and Crohn's disease (CD) have a complex etiology involving multiple genetic and environmental factors. Many genome-wide association studies (GWAS) and subsequent replication studies revealed that both diseases share some of the susceptibility loci; however, common genetic factors for both diseases are not fully elucidated. This study is aimed to identify the common genetic factors for CD and UC by a meta-analysis of published studies. Methods: We first reviewed the 10 GWAS for CD to select candidate single nucleotide polymorphisms (SNPs). Next, we performed a PubMed literature search up to June 30, 2010 and carried out a systemic review of published studies that examined the association of CD susceptibility loci in UC patients. Meta-analysis was carried out using the inverse variance-weighted method or the DerSimonian-Laird method after estimating the heterogeneity among the studies. The data for highly linked SNPs were combined. Finally, we performed a meta-analysis of 43 published studies in 45 SNPs located at 33 loci by using a total of 4852 to 31,125 subjects. Results: We confirmed the association of 17 reported common susceptibility loci. Moreover, we found associations at eight additional loci: GCKR, ATG16L1, CDKAL1, ZNF365, LRRK2-MUC19, C13orf31, PTPN2, and SBNO2. The genetic risk of each locus was modest (odds ratios ranged from 1.05-1.22) except IL23R. Conclusions: These results indicate that CD and UC share many susceptibility loci with small genetic effect. Our data provide further understanding of the common pathogenesis between CD and UC.

AB - Background: Both ulcerative colitis (UC) and Crohn's disease (CD) have a complex etiology involving multiple genetic and environmental factors. Many genome-wide association studies (GWAS) and subsequent replication studies revealed that both diseases share some of the susceptibility loci; however, common genetic factors for both diseases are not fully elucidated. This study is aimed to identify the common genetic factors for CD and UC by a meta-analysis of published studies. Methods: We first reviewed the 10 GWAS for CD to select candidate single nucleotide polymorphisms (SNPs). Next, we performed a PubMed literature search up to June 30, 2010 and carried out a systemic review of published studies that examined the association of CD susceptibility loci in UC patients. Meta-analysis was carried out using the inverse variance-weighted method or the DerSimonian-Laird method after estimating the heterogeneity among the studies. The data for highly linked SNPs were combined. Finally, we performed a meta-analysis of 43 published studies in 45 SNPs located at 33 loci by using a total of 4852 to 31,125 subjects. Results: We confirmed the association of 17 reported common susceptibility loci. Moreover, we found associations at eight additional loci: GCKR, ATG16L1, CDKAL1, ZNF365, LRRK2-MUC19, C13orf31, PTPN2, and SBNO2. The genetic risk of each locus was modest (odds ratios ranged from 1.05-1.22) except IL23R. Conclusions: These results indicate that CD and UC share many susceptibility loci with small genetic effect. Our data provide further understanding of the common pathogenesis between CD and UC.

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