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

当前位置： X-MOL 学术 › Nat. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
Nature Genetics ( IF 31.7 ) Pub Date : 2021-11-05 , DOI: 10.1038/s41588-021-00950-8
Chris Eijsbouts _{1,

2} , Tenghao Zheng _{3,

4} , Nicholas A Kennedy ₅ , Ferdinando Bonfiglio _{3,

4} , Carl A Anderson ₆ , Loukas Moutsianas _{6,

7} , Joanne Holliday ₈ , Jingchunzi Shi ₉ , Suyash Shringarpure ₉ , , Alexandru-Ioan Voda _{10,

11} , , Gianrico Farrugia ₁₂ , Andre Franke ₁₃ , Matthias Hübenthal _{13,

14} , Gonçalo Abecasis ₁₅ , Matthew Zawistowski ₁₅ , Anne Heidi Skogholt _{16,

17} , Eivind Ness-Jensen _{17,

18,

19} , Kristian Hveem ₁₇ , Tõnu Esko ₂₀ , Maris Teder-Laving ₂₀ , Alexandra Zhernakova ₂₁ , Michael Camilleri ₂₂ , Guy Boeckxstaens ₂₃ , Peter J Whorwell ₂₄ , Robin Spiller ₂₅ , Gil McVean ₁ , Mauro D'Amato _{3,

4,

13,

26,

27,

28} , Luke Jostins _{1,

10,

29} , Miles Parkes _{30,

31}

Affiliation

Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Center for Molecular Medicine & Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
School of Biological Sciences, Monash University, Clayton, Victoria, Australia.
IBD Pharmacogenetics, College of Medicine and Health, University of Exeter, Exeter, UK.
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
William Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
23andMe, Inc., Sunnyvale, CA, USA.
Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Saint Edmund Hall, University of Oxford, Oxford, UK.
Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Dermatology, Quincke Research Center, University Hospital Schleswig-Holstein, Kiel, Germany.
Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA.
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
Department of Genetics, University Medical Center Groningen, Groningen, the Netherlands.
Clinical Enteric Neuroscience Translational and Epidemiological Research and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Neurogastroenterology Unit, Wythenshawe Hospital, Centre for Gastrointestinal Sciences, University of Manchester, Manchester, UK.
Nottingham Digestive Diseases Centre, National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
Biodonostia Health Research Institute, San Sebastian, Spain.
Gastrointestinal Genetics Lab, CIC bioGUNE - Basque Research and Technology Alliance, Derio, Spain.
IKERBASQUE, The Basque Science Foundation, Bilbao, Spain.
Christ Church, University of Oxford, Oxford, UK.
Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, UK.
Department of Gastroenterology, Cambridge University Hospital, Cambridge, UK.

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 (r_g > 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.

中文翻译：

对 53,400 名肠易激综合症患者的全基因组分析强调了与情绪和焦虑症的共同遗传途径

肠易激综合症（IBS）是由大脑与肠道相互作用紊乱引起的。识别易感基因可以突出潜在的病理生理机制。我们为英国生物银行设计了一份消化健康调查问卷，并将已识别的肠易激综合症病例与独立队列结合起来。我们对 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 小组（205,252 个病例和 1,384,055 个对照）中复制了显着关联。我们的研究确定并证实了 IBS 的六个遗传易感位点。涉及的基因包括NCAM1 、 CADM2 、 PHF2/FAM120A 、 DOCK9 、 CKAP2/TPTE2P3和BAG6 。前四种与情绪和焦虑障碍有关，在神经系统中表达，或两者兼而有之。与此相呼应的是，我们还发现 IBS 风险与焦虑、神经质和抑郁之间存在很强的全基因组相关性 ( r _g > 0.5)。其他分析表明，这是由于共同的致病途径而引起的，而不是例如焦虑引起腹部症状。所涉及的机制需要进一步探索，以帮助理解 IBS 背后改变的脑-肠相互作用。

更新日期：2021-11-05

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11