The genetic regulation of the gastric transcriptome is associated with metabolic and obesity-related traits and diseases

被引：0

作者：

Koebbe, Laura L. ^{[1
]}

Hess, Timo ^{[1
]}

Giel, Ann-Sophie ^{[1
]}

Bigge, Jessica ^{[1
]}

Gehlen, Jan ^{[1
]}

Schueller, Vitalia ^{[1
]}

Geppert, Michael ^{[2
]}

Dumoulin, Franz Ludwig ^{[3
]}

Heller, Joerg ^{[4
]}

Schepke, Michael ^{[5
]}

Plassmann, Dominik ^{[6
]}

Vieth, Michael ^{[7
]}

Venerito, Marino ^{[8
]}

Schumacher, Johannes ^{[1
]}

Maj, Carlo ^{[1
]}

机构：

[1] Univ Marburg, Ctr Human Genet, Marburg, Germany

[2] Gastroenterol Ctr Dr Geppert, Bayreuth, Germany

[3] St Elisabeth Hosp Bonn, Dept Gastroenterol, Bonn, Germany

[4] Marienhaus Hosp Ahrweiler, Ahrweiler, Germany

[5] Helios Hosp Siegburg, Dept Gastroenterol, Siegburg, Germany

[6] Gastroenterol Ctr Dr Plassmann, Bonn, Germany

[7] Univ Erlangen Nurnberg, Inst Pathol, Klinikum Bayreuth, Bayreuth, Germany

[8] Otto von Guericke Univ Hosp, Dept Gastroenterol Hepatol & Infect Dis, Magdeburg, Germany

来源：

PHYSIOLOGICAL GENOMICS | 2024年 / 56卷 / 05期

关键词：

expression quantitative trait loci; gene expression; metabolism; stomach; R PACKAGE; PHYSIOLOGY; EXPRESSION; BIOLOGY; EQTL; SET;

D O I：

10.1152/physiolgenomics.00120.2023

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Tissue-specific gene expression and gene regulation lead to a better understanding of tissue-specific physiology and pathophysiology. We analyzed the transcriptome and genetic regulatory profiles of two distinct gastric sites, corpus and antrum, to identify tissue-specific gene expression and its regulation. Gastric corpus and antrum mucosa biopsies were collected during routine gastroscopies from up to 431 healthy individuals. We obtained genotype and transcriptome data and performed transcriptome profiling and expression quantitative trait locus (eQTL) studies. We further used data from genome-wide association studies (GWAS) of various diseases and traits to partition their heritability and to perform transcriptome-wide association studies (TWAS). The transcriptome data from corpus and antral mucosa highlights the heterogeneity of gene expression in the stomach. We identified enriched pathways revealing distinct and common physiological processes in gastric corpus and antrum. Furthermore, we found an enrichment of the single nucleotide polymorphism (SNP)-based heritability of metabolic, obesity-related, and cardiovascular traits and diseases by considering corpus- and antrum-specifically expressed genes. Particularly, we could prioritize gastric-specific candidate genes for multiple metabolic traits, like NQO1 which is involved in glucose metabolism, MUC1 which contributes to purine and protein metabolism or RAB27B being a regulator of weight and body composition. Our findings show that gastric corpus and antrum vary in their transcriptome and genetic regulatory profiles indicating physiological differences which are mostly related to digestion and epithelial protection. Moreover, our findings demonstrate that the genetic regulation of the gastric transcriptome is linked to biological mechanisms associated with metabolic, obesity-related, and cardiovascular traits and diseases.

引用

页码：384 / 396

页数：13

共 59 条

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