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A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population

Nature Genetics volume 44, pages 430–434 (2012)Cite this article

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Abstract

Through a genome-wide association analysis with a total of 7,035 individuals with duodenal ulcer and 25,323 controls from Japan, we identified two susceptibility loci at the PSCA gene (encoding prostate stem cell antigen) at 8q24 and at the ABO blood group locus at 9q34. The C allele of rs2294008 at PSCA was associated with increased risk of duodenal ulcer (odds ratio (OR) = 1.84; P = 3.92 × 10−33) in a recessive model but was associated with decreased risk of gastric cancer (OR = 0.79; P = 6.79 × 10−12), as reported previously1. The T allele of rs2294008 encodes a translation initiation codon upstream of the reported site and changes protein localization from the cytoplasm to the cell surface. rs505922 at ABO was also associated with duodenal ulcer in a recessive model (OR = 1.32; P = 1.15 × 10−10). Our findings demonstrate a role for genetic variants in the pathogenesis of duodenal ulcer.

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Figure 1: Manhattan plot showing genome-wide P values of association.
Figure 2: Regional association plots.
Figure 3: Effects of rs2294008 on subcellular localization and stability of PSCA protein.

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Acknowledgements

We thank all the subjects and the members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan, who donated their DNA for this work. We also thank A. Matsui and H. Tagaya and the technical staff of the Laboratory for Genotyping Development at the Center for Genomic Medicine at RIKEN for their technical support. This work was conducted as a part of the BioBank Japan Project, which was supported by the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government.

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Authors and Affiliations

  1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Chizu Tanikawa, Yuji Urabe, Yusuke Nakamura & Koichi Matsuda

  2. Divison of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan

    Keitaro Matsuo, Hidemi Ito & Kazuo Tajima

  3. Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan

    Michiaki Kubo, Atsushi Takahashi & Naoyuki Kamatani

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  1. Chizu Tanikawa
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Contributions

C.T., Y.N. and K. Matsuda conceived and designed the study. Y.U., K. Matsuo and M.K. performed genotyping. A.T. and N.K. performed quality control analysis for the GWAS. Y.N., K. Matsuda and M.K. managed DNA samples belonging to BioBank Japan. H.I. and K.T. managed DNA samples from the Aichi Cancer Center. C.T. analyzed and summarized all the results. C.T., Y.N. and K. Matsuda wrote the manuscript. Y.N. obtained funding for the study.

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Correspondence to Koichi Matsuda.

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Tanikawa, C., Urabe, Y., Matsuo, K. et al. A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population. Nat Genet 44, 430–434 (2012). https://doi.org/10.1038/ng.1109

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