title: Use of genome-wide association studies for cancer research and drug repositioning.
abstract: Although genome-wide association studies have identified many risk loci associated with colorectal cancer, the molecular basis of these associations are still unclear. We aimed to infer biological insights and highlight candidate genes of interest within GWAS risk loci. We used an in silico pipeline based on functional annotation, quantitative trait loci mapping of cis-acting gene, PubMed text-mining, protein-protein interaction studies, genetic overlaps with cancer somatic mutations and knockout mouse phenotypes, and functional enrichment analysis to prioritize the candidate genes at the colorectal cancer risk loci. Based on these analyses, we observed that these genes were the targets of approved therapies for colorectal cancer, and suggested that drugs approved for other indications may be repurposed for the treatment of colorectal cancer. This study highlights the use of publicly available data as a cost effective solution to derive biological insights, and provides an empirical evidence that the molecular basis of colorectal cancer can provide important leads for the discovery of new drugs.
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Jizhun
authors: J
authors: Zhang
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Kewei
authors: K
authors: Jiang
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Liang
authors: L
authors: Lv
authors: Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Hui
authors: H
authors: Wang
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Zhanlong
authors: Z
authors: Shen
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Zhidong
authors: Z
authors: Gao
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Bo
authors: B
authors: Wang
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Yingjiang
authors: Y
authors: Ye
authors: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, 100044, PR China.
authors: Shan
authors: S
authors: Wang
mesh_terms: D000483:Alleles; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D058492:Drug Repositioning; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D023281:Genomics / Q000379:methods; D006801:Humans; D058977:Molecular Sequence Annotation; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D040641:Quantitative Trait Loci