A new method for post Genome-Wide Association Study (GWAS) analysis of colorectal cancer in Taiwan

Hwei Ming Wang, Tzu Hao Chang, Feng Mao Lin, Te Hsin Chao, Wei Chih Huang, Chao Liang, Chao Fang Chu, Chih Min Chiu, Wei Yun Wu, Ming Cheng Chen, Chen Tsung Weng, Shun Long Weng, Feng Fan Chiang, Hsien Da Huang

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7 Citations (Scopus)

Abstract

Recently, single nucleotide polymorphisms (SNPs) located in specific loci or genes have been identified associated with susceptibility to colorectal cancer (CRC) in Genome-Wide Association Studies (GWAS). However, in different ethnicities and regions, the genetic variations and the environmental factors can widely vary. Therefore, here we propose a post-GWAS analysis method to investigate the CRC susceptibility SNPs in Taiwan by conducting a replication analysis and bioinformatics analysis. One hundred and forty-four significant SNPs from published GWAS results were collected by a literature survey, and two hundred and eighteen CRC samples and 385 normal samples were collected for post-GWAS analysis. Finally, twenty-six significant SNPs were identified and reported as associated with susceptibility to colorectal cancer, other cancers, obesity, and celiac disease in a previous GWAS study. Functional analysis results of 26 SNPs indicate that most biological processes identified are involved in regulating immune responses and apoptosis. In addition, an efficient prediction model was constructed by applying Jackknife feature selection and ANOVA testing. As compared to another risk prediction model of CRC for European Caucasians population, which performs 0.616 of AUC by using 54 SNPs, the proposed model shows good performance in predicting CRC risk within the Taiwanese population, i.e., 0.724 AUC by using 16 SNPs. We believe that the proposed risk prediction model is highly promising for predicting CRC risk within the Taiwanese population. In addition, the functional analysis results could be helpful to explore the potential associated regulatory mechanisms that may be involved in CRC development.

Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalGene
Volume518
Issue number1
DOIs
Publication statusPublished - Apr 10 2013

Keywords

  • Colorectal cancer
  • Genome-Wide Association Studies
  • GWAS
  • Risk prediction
  • Single-nucleotide polymorphism
  • SNP

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Wang, H. M., Chang, T. H., Lin, F. M., Chao, T. H., Huang, W. C., Liang, C., Chu, C. F., Chiu, C. M., Wu, W. Y., Chen, M. C., Weng, C. T., Weng, S. L., Chiang, F. F., & Huang, H. D. (2013). A new method for post Genome-Wide Association Study (GWAS) analysis of colorectal cancer in Taiwan. Gene, 518(1), 107-113. https://doi.org/10.1016/j.gene.2012.11.067