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. 2025 Oct;15(10):e70489.
doi: 10.1002/ctm2.70489.

Genetic architecture of gastric adenocarcinoma in West Asia

Saeid Latifi-Navid  1 , Esmat Abdi  1 , Tianpei Wang  2   3 , Farhad Pourfarzi  4 , Abbas Yazdanbod  4 , Seyed Alireza Salami  5   6 , Reza Safaralizadeh  7 , Omolbanin Amjadi  8 , Hamid Latifi-Navid  9 , Bahareh Safarnejad  10 , Mahmoud Shokrabadi  11 , Iradj Maleki  12 , Vahid Hosseini  12 , Seyed Mohammad Valizadeh  12 , Mehdi Pourghasemian  13 , Negin Abediasl  4 , Arash Kazemi  12 , Mohammad Eslami Jouybari  8 , Zohreh Bari  12 , Tarang Taghvaei  12 , Caiwang Yan  14   15   16 , Amir Taher Eftekhar Sadat  17 , Seyed Yaghoub Moaddab  18 , Ghasem Janbabaei  19 , Mohammad Hossein Somi  18 , Alireza Sadjadi  20 , Ramin Shakeri  20 , Farideh Siavoshi  21 , Hafez Fakheri  12 , Hossein Poustchi  20 , Reza Malekzadeh  20 , Guangfu Jin  14   15   16
Affiliations

Genetic architecture of gastric adenocarcinoma in West Asia

Saeid Latifi-Navid et al. Clin Transl Med. 2025 Oct.
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Study design and workflow. (B) Manhattan plots from GWAS and MAGMA gene‐based analyses. (A) Manhattan plot of the GWAS analysis of gastric cancer, showing the negative log10‐transformed p‐value for each SNP. (B) Manhattan plot of the gene‐based test results computed by MAGMA. The input SNPs were mapped to 19351 protein‐coding genes. Genome‐wide significance (red dashed line in the plot) was defined at p = .05/19 351 = 2.58 × 10−6. A total of 13 genes were identified as significantly associated with GC risk. Among these were MTX1, THBS3, MUC1, TRIM46, RP11‐201K10.3, and KRTCAP2, which were located on chromosome 1. Additionally, LY6K, LYPD2, SLURP1, LYNX1, THEM6, PSCA, and LY6D were located on chromosome 8. On the y‐axis, the gene‐based test's negative log10‐transformed p‐value is displayed, and on the x‐axis, the starting position on the chromosome is shown.
FIGURE 2
FIGURE 2
Regional plots of five novel gastric cancer susceptibility loci on 1p33, 3p22.1, 3p11.1, 10q25.2, and 17q21.31. Association p‐values from a trend test are displayed in –log10 (y axis) for each single‐nucleotide polymorphism according to their chromosomal positions (x‐axis) at (A) 1p33 (rs498352), (B) 3p11.1 (rs4859012), (C) 3p22.1 (rs11720364), (D) 10q25.2 (rs7899485), and (E) 17q21.31 (rs114469358). SNPs are coloured by their highest r 2 compared with one of the independent significant SNPs. Other SNPs are coloured in grey. The top lead SNPs in genomic risk loci, lead SNPs and independent significant SNPs are circled in black and coloured dark‐purple, purple and red, respectively. Pairwise r 2 values are from 1000G phase 3 data. SNPs were mapped to genes by physical distance from known genes encoding proteins in the human reference assembly (GRCh37/hg19).
FIGURE 3
FIGURE 3
Bayesian colocalization analysis of significant GWAS findings. Colocalization analysis was carried out for the six reported (replicated) and 28 novel loci from GWASs in stomach tissue from GTEx v8. For each gene of a region, a posterior probability was obtained; the greater the posterior probability was (PP4 > .7), the stronger the evidence for colocalization. (A–C) Three loci, 1q22, 4q28.1, and 8q24.3, colocalised with eQTLs in stomach tissue (>.7). The regional lead SNPs were cis‐associated with gene expression (lower right) and simultaneously associated with facial variation in the GWAS (upper right). Therefore, these SNPs contribute to both cis‐eQTL signals and GWAS signals (left). (D, E) The novel loci, however, did show some potential colocalization signals (especially for 11q14.1 and 13q14.11), but the PP4 of colocalization was <.7.
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