학술논문
Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
Document Type
article
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; Hübenthal, Matthias; Abecasis, Gonçalo; Zawistowski, Matthew; Skogholt, Anne Heidi; Ness-Jensen, Eivind; Hveem, Kristian; Esko, Tõnu; Teder-Laving, Maris; Zhernakova, Alexandra; Camilleri, Michael; Boeckxstaens, Guy; Whorwell, Peter J; Spiller, Robin; McVean, Gil; D’Amato, Mauro; Jostins, Luke; Parkes, Miles
Source
Nature Genetics. 53(11)
Subject
Language
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.