Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.

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Hdl Handle:
http://hdl.handle.net/11287/620175
Title:
Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.
Authors:
de Lange, K. M.; Moutsianas, L.; Lee, J. C.; Lamb, C. A.; Luo, Y.; Kennedy, Nicholas A.; Jostins, L.; Rice, D. L.; Gutierrez-Achury, J.; Ji, S.-G.; Heap, Graham A.; Nimmo, E. R.; Edwards, C.; Henderson, P.; Mowat, C.; Sanderson, J.; Satsangi, J.; Simmons, A.; Wilson, D. C.; Tremelling, M.; Hart, A.; Mathew, C. G.; Newman, W. G.; Parkes, M.; Lees, C. W.; Uhlig, H.; Hawkey, C.; Prescott, N. J.; Ahmad, Tariq; Mansfield, J. C.; Anderson, C. A.; Barrett, J. C.
Abstract:
Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 and ITGB8) and at previously implicated loci (ITGAL and ICAM1). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2, and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.
Citation:
Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. 2017 Feb;49(2):256-261. Epub 9 Jan, Nat. Genet.
Publisher:
Nature
Journal:
Nature Genetics
Issue Date:
9-Jan-2017
URI:
http://hdl.handle.net/11287/620175
DOI:
10.1038/ng.3760
PubMed ID:
28067908
Additional Links:
http://dx.doi.org/10.1038/ng.3760
Type:
Letter
Language:
en
ISSN:
1546-1718
Appears in Collections:
Gastroenterology; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorde Lange, K. M.en
dc.contributor.authorMoutsianas, L.en
dc.contributor.authorLee, J. C.en
dc.contributor.authorLamb, C. A.en
dc.contributor.authorLuo, Y.en
dc.contributor.authorKennedy, Nicholas A.en
dc.contributor.authorJostins, L.en
dc.contributor.authorRice, D. L.en
dc.contributor.authorGutierrez-Achury, J.en
dc.contributor.authorJi, S.-G.en
dc.contributor.authorHeap, Graham A.en
dc.contributor.authorNimmo, E. R.en
dc.contributor.authorEdwards, C.en
dc.contributor.authorHenderson, P.en
dc.contributor.authorMowat, C.en
dc.contributor.authorSanderson, J.en
dc.contributor.authorSatsangi, J.en
dc.contributor.authorSimmons, A.en
dc.contributor.authorWilson, D. C.en
dc.contributor.authorTremelling, M.en
dc.contributor.authorHart, A.en
dc.contributor.authorMathew, C. G.en
dc.contributor.authorNewman, W. G.en
dc.contributor.authorParkes, M.en
dc.contributor.authorLees, C. W.en
dc.contributor.authorUhlig, H.en
dc.contributor.authorHawkey, C.en
dc.contributor.authorPrescott, N. J.en
dc.contributor.authorAhmad, Tariqen
dc.contributor.authorMansfield, J. C.en
dc.contributor.authorAnderson, C. A.en
dc.contributor.authorBarrett, J. C.en
dc.date.accessioned2017-01-17T10:22:37Z-
dc.date.available2017-01-17T10:22:37Z-
dc.date.issued2017-01-09-
dc.identifier.citationGenome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. 2017 Feb;49(2):256-261. Epub 9 Jan, Nat. Genet.en
dc.identifier.issn1546-1718-
dc.identifier.pmid28067908-
dc.identifier.doi10.1038/ng.3760-
dc.identifier.urihttp://hdl.handle.net/11287/620175-
dc.description.abstractGenetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 and ITGB8) and at previously implicated loci (ITGAL and ICAM1). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2, and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/ng.3760en
dc.rightsArchived with thanks to Nature Geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Gastroenterologyen
dc.titleGenome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.en
dc.typeLetteren
dc.identifier.journalNature Geneticsen
dc.type.versionIn press (epub ahead of print)en

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