Pathway analysis of expression-related SNPs on genome-wide association study of basal cell carcinoma

Xin Li, Liming Liang, Immaculata De Vivo, Jean Y. Tang, Jiali Han

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Genome-wide association studies (GWASs) have primarily focused on the association between individual genetic markers and risk of disease. We applied a novel approach that integrates skin expression-related single-nucleotide polymorphisms (eSNPs) and pathway analysis for GWAS of basal cell carcinoma (BCC) to identify potential novel biological pathways. We evaluated the associations between 70,932 skin eSNPs and risk of BCC among 2,323 cases and 7,275 controls of European ancestry, and then assigned them to the pathways defined by KEGG, GO, and BioCarta databases. Three KEGG pathways (colorectal cancer, actin cytoskeleton, and BCC), two GO pathways (cellular component disassembly in apoptosis, and nucleus organization), and four BioCarta pathways (Ras signaling, T cell receptor signaling, natural killer cell-mediated cytotoxicity, and links between Pyk2 and Map Kinases) showed significant association with BCC risk with p-value < 0.05 and FDR < 0.2. These pathways also ranked at top in sensitivity analyses. Two positive controls in KEGG, the hedgehog pathway and the BCC pathway, showed significant association with BCC risk in both main and sensitivity analyses. Our results indicate that SNPs that are undetectable by conventional GWASs are significantly associated with BCC when tested as pathways. Biological studies of these gene groups suggest their potential roles in the etiology of BCC.

Original languageEnglish (US)
Pages (from-to)36885-36895
Number of pages11
JournalOncotarget
Volume7
Issue number24
DOIs
StatePublished - Jan 1 2016

Fingerprint

Genome-Wide Association Study
Basal Cell Carcinoma
Single Nucleotide Polymorphism
Skin
T-Cell Antigen Receptor
Actin Cytoskeleton
Genetic Markers
Natural Killer Cells
Colorectal Neoplasms
Phosphotransferases
Databases
Apoptosis
Genes

Keywords

  • Basal cell carcinoma (BCC)
  • Expression-related SNPs (eSNPs)
  • Genome-wide association study (GWAS)
  • Pathway analysis
  • Pathway databases

ASJC Scopus subject areas

  • Oncology

Cite this

Pathway analysis of expression-related SNPs on genome-wide association study of basal cell carcinoma. / Li, Xin; Liang, Liming; De Vivo, Immaculata; Tang, Jean Y.; Han, Jiali.

In: Oncotarget, Vol. 7, No. 24, 01.01.2016, p. 36885-36895.

Research output: Contribution to journalArticle

Li, Xin ; Liang, Liming ; De Vivo, Immaculata ; Tang, Jean Y. ; Han, Jiali. / Pathway analysis of expression-related SNPs on genome-wide association study of basal cell carcinoma. In: Oncotarget. 2016 ; Vol. 7, No. 24. pp. 36885-36895.
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