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

Publication: Nature Genetics

Chris Eijsbouts, Tenghao Zheng, Nicholas A. Kennedy, Ferdinando Bonfiglio, Carl A. Anderson, Loukas Moutsianas, Joanne Holliday, Jingchunzi Shi, Suyash Shringarpure, 23andMe Research Team, Alexandru-Ioan Voda, The Bellygenes Initiative, Gianrico Farrugia, Andre Franke, Matthias Hübenthal, Gonçalo Abecasis, Matthew Zawistowski, Anne Heidi Skogholt, Eivind Ness-Jensen, Kristian Hveem, Tõnu Esko, Maris Teder-Laving, Alexandra Zhernakova, Michael Camilleri, Guy Boeckxstaens, Peter J. Whorwell, Robin Spiller, Gil McVean, Mauro D’Amato,
Luke Jostins & Miles Parkes

05 November 2021


Summary

An international study of more than 50,000 people with irritable bowel syndrome (IBS) has revealed that IBS symptoms may be caused by the same biological processes as conditions such as anxiety.

The research team, including more than 40 institutions showed that overall, heritability of IBS (how much your genes influence the likelihood of developing a particular condition) is quite low, indicating the importance of environmental factors such as diet, stress and patterns of behaviour that may also be shared in the family environment.

However, 6 genetic differences were more common in people with IBS than in controls. Researchers found most of the altered genes appear to have more clear-cut roles in the brain and possibly the nerves which supply the gut, rather than the gut itself.

The team also looked for overlap between susceptibility to IBS and other physical and mental health conditions.  They found that the same genetic make-up that puts people at increased risk of IBS also increases the risk for common mood and anxiety disorders such as anxiety, depression, and neuroticism, as well as insomnia. However,  this doesn’t mean that anxiety causes IBS symptoms or vice versa.

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A blood-based prognostic biomarker in IBD

Publication: Gut

Daniele Biasci, James C Lee Nurulamin M Noor, Diana R Pombal, Monica Hou, Nina Lewis, Tariq Ahmad, Ailsa Hart, Miles Parkes, Eoin F McKinney, Paul A Lyons, Kenneth G C Smith

1 October 2019


Summary:

Researchers have previously described a prognostic transcriptional signature in CD8 T cells that separates patients with IBD into two phenotypically distinct subgroups, termed IBD1 and IBD2. They sought to develop a blood-based test that could identify these subgroups without cell separation, and would be suitable for clinical use in Crohn’s disease (CD) and ulcerative colitis (UC).

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Somatic mutations and clonal dynamics in healthy and cirrhotic human liver

Publication: Nature

Simon F Brunner, Nicola D Roberts, Luke A Wylie, Luiza Moore, Sarah J Aitken, Susan E Davies, Mathijs A Sanders , Pete Ellis, Chris Alder, Yvette Hooks, Federico Abascal, Michael R Stratton, Inigo Martincorena, Matthew Hoare, Peter J Campbell

23 October 2019


Summary:

The most common causes of chronic liver disease are excess alcohol intake, viral hepatitis and non-alcoholic fatty liver disease.

The genome of HCC exhibits diverse mutational signatures, resulting in recurrent mutations across more than 30 cancer genes. Stem cells from normal livers have a low mutational burden and limited diversity of signatures, which suggests that the complexity of HCC arises during the progression to chronic liver disease and subsequent malignant transformation.

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FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle

Publication: Cell

M. Zaeem Cader, Rodrigo Pereira de Almeida Rodrigues, James A. West, Gavin W. Sewell, Muhammad N. Md-Ibrahim, Stephanie Reikine, Giuseppe Sirago, Lukas W. Unger, Ana Belén Iglesias-Romero, Katharina Ramshorn, Lea-Maxie Haag, Svetlana Saveljeva, Jana-Fabienne Ebel, Philip Rosenstiel, Nicole C. Kaneider, James C. Lee, Trevor D. Lawley, Allan Bradley, Gordon Dougan, Yorgo Modis, Julian L. Griffin, Arthur Kaser

23 January 2020


Summary

Mutations in FAMIN cause arthritis and inflammatory bowel disease in early childhood, and a common genetic variant increases the risk for Crohn’s disease and leprosy. Researchers developed an unbiased liquid chromatography-mass spectrometry screen for enzymatic activity of this orphan protein.

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Somatic Evolution in Non-neoplastic IBDAffected Colon

Publication: Cell

Olafsson S, McIntyre RE, Coorens T, Butler T, Jung H, Robinson PS, Lee-Six H, Sanders MA, Arestang K, Dawson C, Tripathi M. Somatic evolution in non-neoplastic IBD-affected colon.

6 August 2020


Summary

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers. We whole-genome sequenced 446 colonic crypts (intestinal glands in the colon) from 46 IBD patients and compared these to 412 crypts from 41 non-IBD controls from our previous publication on the mutation landscape of the normal colon.

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Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study

Publication: The Lancet

Kennedy NA, Heap GA, Green HD, Hamilton B, Bewshea C, Walker GJ, Thomas A, Nice R, Perry MH, Bouri S, Chanchlani N, Heerasing NM, Hendy P, Lin S, Gaya DR, Cummings JRF, Selinger CP, Lees CW, Hart AL, Parkes M, Sebastian S, Mansfield JC, Irving PM, Lindsay J, Russell RK, McDonald TJ, McGovern D, Goodhand JR, Ahmad T; UK Inflammatory Bowel Disease Pharmacogenetics Study Group.

26 February 2019

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Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease

Publication: JAMA

Walker GJ, Harrison JW, Heap GA, Voskuil MD, Andersen V, Anderson CA, Ananthakrishnan AN, Barrett JC, Beaugerie L, Bewshea CM, Cole AT, Cummings FR, Daly MJ, Ellul P, Fedorak RN, Festen EAM, Florin TH, Gaya DR, Halfvarson J, Hart AL, Heerasing NM, Hendy P, Irving PM, Jones SE, Koskela J, Lindsay JO, Mansfield JC, McGovern D, Parkes M, Pollok RCG, Ramakrishnan S, Rampton DS, Rivas MA, Russell RK, Schultz M, Sebastian S, Seksik P, Singh A, So K, Sokol H, Subramaniam K, Todd A, Annese V, Weersma RK, Xavier R, Ward R, Weedon MN, Goodhand JR, Kennedy NA, Ahmad T; IBD Pharmacogenetics Study Group.

26 February 2019

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Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial.

Publication: BMJ Open

Thomas MG, Bayliss C, Bond S, Dowling F, Galea J, Jairath V, Lamb C, Probert C, Timperley-Preece E, Watson A, Whitehead L, Williams JG, Parkes M, Kaser A, Raine T.

15 February 2019

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ACG Clinical Guideline for Alcoholic Liver Disease: The MELD Threshold for Corticosteroid Treatment has Yet to be Established

Publication: American Journal of Gastroenterology

Forrest EH, Atkinson SR, Richardson P, Masson S, Ryder S, Thursz MR, Allison M.

2019 Jan;114(1):175-176.

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Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

Publication: Gastroenterology

Eddowes PJ, Sasso M, Allison M, Tsochatzis E, Anstee QM, Sheridan D, Guha IN, Cobbold JF, Deeks JJ, Paradis V, Bedossa P, Newsome PN.

25 January 2019

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