一个基因或变异体具有多效性作用，跨多个表型的遗传变异鉴定可以提供不同疾病或表型共享的生物通路的综合理解。发现与多种疾病相关的基因位点可以同时支持一般干预。几个元分析已经显示了与胃癌相关的遗传关联；然而，没有任何研究使用这种方法鉴定与其他表型的关联。 在这里，我们应用了疾病网络分析和基于基因的分析（GBA）来研究与胃癌相关的遗传变异体，同时与其他表型相关联。我们通过系统性全基因组关联研究（GWAS）与胃癌相关联的单核苷酸多态性（SNP）水平元分析和 GBA，将已发表的 SNP 变异体结果集成在一起，并将它们分成主要的与胃癌相关的基因。然后，我们进行疾病网络和表达性状定量基因位点（eQTL）分析，以评估跨表型关联和与胃癌相关的基因的表达水平。 共有七个基因（MTX1、GBAP1、MUC1、TRIM46、THBS3、PSCA 和 ABO）与胃癌以及血尿素氮（BUN）、肾小球滤过率（GFR）和尿酸（UA）相关联。此外，17 个 SNPs 调节了位于 1q22 上的基因的表达，24 个 SNPs 调节了位于 8q24.3 上的 PSCA 的表达，rs7849820 调节了位于 9q34.2 上的 ABO 的表达。此外，rs1057941 和 rs2294008 在 1q22 和 8q24.3 中具有最高的后验概率，成为潜在的影响性 SNP 候选。 这些发现确定了七个与胃癌相关的基因，表现出与 GFR、BUN 和 UA 的交叉关联。© 2023年。作者在国际胃癌协会和日本胃癌协会的独家许可下。

A gene or variant has pleiotropic effects, and genetic variant identification across multiple phenotypes can provide a comprehensive understanding of biological pathways shared among different diseases or phenotypes. Discovery of genetic loci associated with multiple diseases can simultaneously support general interventions. Several meta-analyses have shown genetic associations with gastric cancer (GC); however, no study has identified associations with other phenotypes using this approach.Here, we applied disease network analysis and gene-based analysis (GBA) to examine genetic variants linked to GC and simultaneously associated with other phenotypes. We conducted a single-nucleotide polymorphism (SNP) level meta-analysis and GBA through a systematic genome-wide association study (GWAS) linked to GC, to integrate published results for the SNP variants and group them into major GC-associated genes. We then performed disease network and expression quantitative trait loci (eQTL) analyses to evaluate cross-phenotype associations and expression levels of GC-related genes.Seven genes (MTX1, GBAP1, MUC1, TRIM46, THBS3, PSCA, and ABO) were associated with GC as well as blood urea nitrogen (BUN), glomerular filtration rate (GFR), and uric acid (UA). In addition, 17 SNPs regulated the expression of genes located on 1q22, 24 SNPs regulated the expression of PSCA on 8q24.3, and rs7849820 regulated the expression of ABO on 9q34.2. Furthermore, rs1057941 and rs2294008 had the highest posterior causal probabilities of being a causal candidate SNP in 1q22, and 8q24.3, respectively.These findings identified seven GC-associated genes exhibiting a cross-association with GFR, BUN, and UA.© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.