日本东京大学Yoichiro Kamatani研究团队发现东亚特异性和跨祖先全基因组荟萃分析提供了消化性溃疡病(PUD)的机制见解。该项研究成果发表在2023年11月30日出版的《自然—遗传学》上。

他们对PUD进行了大规模的跨祖先荟萃分析，结合全基因组关联研究与日本和欧洲的研究(52,032例病例和905,344例对照)，发现了25个新的基因座在祖先之间高度一致。对胃溃疡(GU)和十二指肠溃疡(DU)遗传结构的研究表明，GUs与DUs具有相同的风险位点，尽管遗传效应较小，多基因性高于DUs，表明GUs具有更高的异质性。幽门螺杆菌(HP)-分层分析发现一个HP相关宿主遗传位点。

使用整体和单细胞转录组谱的综合分析强调了胃组织中富含高表达基因的PUD遗传因素，特别是在产生生长抑素的D细胞中。他们的研究结果提供了遗传学证据，表明胃肠细胞分化和激素调节在PUD病因学中至关重要。

据介绍，PUD是指胃酸引起的消化道损伤，主要发生在胃(GU)或十二指肠(DU)。

附：英文原文

Title: East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease

Author: He, Yunye, Koido, Masaru, Sutoh, Yoichi, Shi, Mingyang, Otsuka-Yamasaki, Yayoi, Munter, Hans Markus, Morisaki, Takayuki, Nagai, Akiko, Murakami, Yoshinori, Tanikawa, Chizu, Hachiya, Tsuyoshi, Matsuda, Koichi, Shimizu, Atsushi, Kamatani, Yoichiro

Issue&Volume: 2023-11-30

Abstract: Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)). In the present study, we conducted a large-scale, cross-ancestry meta-analysis of PUD combining genome-wide association studies with Japanese and European studies (52,032 cases and 905,344 controls), and discovered 25 new loci highly concordant across ancestries. An examination of GU and DU genetic architecture demonstrated that GUs shared the same risk loci as DUs, although with smaller genetic effect sizes and higher polygenicity than DUs, indicating higher heterogeneity of GUs. Helicobacter pylori (HP)-stratified analysis found an HP-related host genetic locus. Integrative analyses using bulk and single-cell transcriptome profiles highlighted the genetic factors of PUD being enriched in the highly expressed genes in stomach tissues, especially in somatostatin-producing D cells. Our results provide genetic evidence that gastrointestinal cell differentiations and hormone regulations are critical in PUD etiology.

DOI: 10.1038/s41588-023-01569-7

Source: https://www.nature.com/articles/s41588-023-01569-7