Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.
Details
Serval ID
serval:BIB_31F78CA4D9D3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.
Journal
Nature communications
Working group(s)
COLORS in IBD group investigators, Oxford IBD cohort study investigators, INTERVAL Study, Swiss IBD cohort investigators, UK IBD Genetics Consortium, NIDDK IBD Genetics Consortium
Contributor(s)
Zurek M., Strisciuglio C., Elawad M., Lo B., Arancibia-Carcamo C., Bailey A., Barnes E., Bird-Lieberman E.L., Brain O., Braden B., Collier J., East J., Howarth L., Keshav S., Klenerman P., Leedham S., Palmer R., Powrie F., Simmons A., Walker M., Tolkien Z., Kaptoge S., Allen D., Mehenny S., Mant J., Di Angelantonio E., Thompson S.G., Yilmaz B., Juillerat P., Geuking M., Wiest R., Macpherson A.J., Bravo F.D., Brügger L., Carstens O., Bigler U.G., Heimgartner B., Rusticeanu M., Schmid-Uebelhart S., Strebel B., Tatu A., Tutuian R., Wiest R., Øyås O., Ramon C., Stelling J., Franc Y., Fournier N., Pittet VEH, Burnand B., Egger M., Franc Y., Golay D., Marot A., Musso L., Pittet V., Rossel J.B., Seematter V., Sommer J., Vulliamy R., Michetti P., Maillard M.H., Keller C., Maillard M.H., Nydegger A., Schoepfe A., Archanioti E., Ezri J., Fraga M., Schoepfer A., Müller C., Rogler G., Biedermann L., Blattmann M., Burk S., Dora B., Fried M., Misselwitz B., Müllhaupt B., Obialo N., Pohl D., Raschle N., Rogler G., Scharl M., Vavricka S., Von Känel R., Zeitz J., Abdelrahman K., Ademi G., Borovicka J., Brand S., Frei R., Haarer J., Knellwolf-Grieger C., Krieger-Grübel C., Künzler P., Meyenberger C., Meyer P., Röhrich N., Sawatzki M., Schelling M., Semadeni G.M., Sulz M., Zimmermann D., Aepli P., Criblez D.H., Hess C., Richterich J.P., Spalinger J., Staudenmann D., Stulz A., Wöhrle S., Thomas A., Anderegg C., Köhler H., Kusche R., Antonino A.T., Arrigoni E., Bengoa J.M., Cunningham S., de Saussure P., Girard L., de Jong D.B., Bastürk P., Brunner S., Degen L., Hruz P., Bakker C.K., Niess J., Balsiger B., Haldemann J., Saner G., Seibold F., Bauerfeind P., Becocci A., Belli D., Binek J., Hengstler P., Boehm S., Boldanov T., Bühr P., Koller R., Rueger V., Senning A., Burri E., Buyse S., Cao D.T., D'Angelo F., Delarive J., Doerig C., Hessler R., Preissler C., Rentsch R., Risti B., Ritz M.A., Steuerwald M., Vögtlin J., Sagmeister M., Sauter B., Schibli S., Sokollik C., Spalinger J., Schlauri H., Schnegg J.F., Seirafi M., Spangenberger H., Stadler P., Staub P., Stenz V., Tempia-Caliera M., Thorens J., Truninger K., Urfer P., Viani F., Vouillamoz D., Zander S., Wyli T., Jostins L., Kennedy N.A., Ahmad T., Lamb C.A., Edwards C., Hart A., Hawkey C., Mansfield J.C., Mowat C., Newman W.G., Simmons A., Tremelling M., Lee J.C., Prescott N.J., Mathew C.G., Lees C.W., McGovern DPB, Targan S.R., Botwin G., Mengesha E., Fleshner P., Landers C., Li D., Rioux J.D., Bitton A., Côté-Daigneault J., Daly M.J., Xavier R., Morris K., Boucher G., Cho J.H., Abraham C., Merad M., Sands B., Peter I., Hao K., Itan Y., Duerr R.H., Konnikova L., Schwartz M.B., Proksell S., Johnston E., Miladinova V., Chen W., Brant S.R., Datta L., Silverberg M.S., Schumm L.P., Birch S., Giri M., Gettler K., Sharma Y., Stevens C., Lazarev M., Haritunians T.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
21/02/2020
Peer-reviewed
Oui
Volume
11
Number
1
Pages
995
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10 <sup>-10</sup> ), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10 <sup>-10</sup> ). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.
Keywords
Adult, Age of Onset, Case-Control Studies, Child, Child, Preschool, Cohort Studies, Female, Genes, Recessive, Genetic Predisposition to Disease, Genetic Variation, Humans, Infant, Infant, Newborn, Inflammatory Bowel Diseases/etiology, Inflammatory Bowel Diseases/genetics, Loss of Function Mutation, Male, Mosaicism, Multifactorial Inheritance, Mutation, NADPH Oxidase 2/genetics, Pedigree, Primary Immunodeficiency Diseases/complications, Primary Immunodeficiency Diseases/genetics, Risk Factors, Whole Exome Sequencing
Pubmed
Web of science
Open Access
Yes
Create date
10/09/2020 10:30
Last modification date
21/11/2022 8:22
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