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Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population.

Authors
  • Pyun, Hyojin1, 2
  • Gunathilake, Madhawa2
  • Lee, Jeonghee2
  • Choi, Il Ju3
  • Kim, Young-Il3
  • Sung, Joohon1, 4
  • Kim, Jeongseon2
  • 1 Division of Genome and Health Big Data, Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea. , (North Korea)
  • 2 Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang, Korea. , (North Korea)
  • 3 Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea. , (North Korea)
  • 4 Institute of Health and Environment, Seoul National University, Seoul, Korea. , (North Korea)
Type
Published Article
Journal
Cancer research and treatment
Publication Date
Jan 01, 2024
Volume
56
Issue
1
Pages
191–198
Identifiers
DOI: 10.4143/crt.2022.958
PMID: 37340842
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns. The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed. In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10-83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10-6 (0.05/13,114); DEFB108B had the lowest p=5.94×10-15, followed by FAM86C1 (p=1.74×10-14), PSCA (p=1.81×10-14), and KLHDC4 (p=5.00×10-10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway. While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.

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