英国牛津大学Miles Parkes等研究人员合作对53,400名肠易激综合征患者的全基因组分析突出与情绪和焦虑症相关的共同遗传途径。相关论文发表在2021年11月5日出版的《自然—遗传学》杂志上。

研究人员为英国生物银行设计了一份消化系统健康问卷，并将确定的肠易激综合征（IBS）病例与独立的队列相结合。研究人员对53,400个病例和433,201个对照进行了全基因组关联研究，并在23andMe队列（205,252个病例和1,384,055个对照）中重复了显著关联。研究人员发现并证实了6个IBS的遗传易感位点。涉及的基因包括NCAM1、CADM2、PHF2/FAM120A、DOCK9、CKAP2/TPTE2P3和BAG6。前四个与情绪和焦虑症有关，在神经系统中表达，或两者都有。

与此相呼应，研究人员还发现IBS的风险与焦虑、神经质和抑郁之间有强烈的全基因组相关性（rg>0.5）。其他分析表明，这是由共同的致病途径引起的，而不是例如焦虑导致腹部症状。潜在的机制需要进一步探索，以便帮助理解IBS背后的大脑-肠道相互作用的改变。

据了解，IBS是由大脑与肠道的相互作用紊乱导致的。识别易感基因可以突出潜在的病理生理机制。

附：英文原文

Title: Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Author: Eijsbouts, Chris, Zheng, Tenghao, Kennedy, Nicholas A., Bonfiglio, Ferdinando, Anderson, Carl A., Moutsianas, Loukas, Holliday, Joanne, Shi, Jingchunzi, Shringarpure, Suyash, Voda, Alexandru-Ioan, Farrugia, Gianrico, Franke, Andre, Hbenthal, Matthias, Abecasis, Gonalo, Zawistowski, Matthew, Skogholt, Anne Heidi, Ness-Jensen, Eivind, Hveem, Kristian, Esko, Tnu, Teder-Laving, Maris, Zhernakova, Alexandra, Camilleri, Michael, Boeckxstaens, Guy, Whorwell, Peter J., Spiller, Robin, McVean, Gil, DAmato, Mauro, Jostins, Luke, Parkes, Miles

Issue&Volume: 2021-11-05

Abstract: Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg>0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS.

DOI: 10.1038/s41588-021-00950-8

Source: https://www.nature.com/articles/s41588-021-00950-8