Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620174
Title:
Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7.
Authors:
Luo, Y.; de Lange, K. M.; Jostins, L.; Moutsianas, L.; Randall, J.; Kennedy, N. A.; Lamb, C. A.; McCarthy, S.; Ahmad, Tariq; Edwards, C.; Serra, E. G.; Hart, A.; Hawkey, C.; Mansfield, J. C.; Mowat, C.; Newman, W. G.; Nichols, S.; Pollard, M.; Satsangi, J.; Simmons, A.; Tremelling, M.; Uhlig, H.; Wilson, D. C.; Lee, J. C.; Prescott, N. J.; Lees, C. W.; Mathew, C. G.; Parkes, M.; Barrett, J. C.; Anderson, C. A.
Abstract:
To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn's disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve understanding of the biology of complex diseases.
Citation:
Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7. 2017 Feb;49(2):186-192. Epub Jan 9
Publisher:
Nature
Journal:
Nature Genetics
Issue Date:
9-Jan-2017
URI:
http://hdl.handle.net/11287/620174
DOI:
10.1038/ng.3761
PubMed ID:
28067910
Additional Links:
http://dx.doi.org/10.1038/ng.3761
Type:
Journal Article
Language:
en
ISSN:
1546-1718
Appears in Collections:
Gastroenterology; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLuo, Y.en
dc.contributor.authorde Lange, K. M.en
dc.contributor.authorJostins, L.en
dc.contributor.authorMoutsianas, L.en
dc.contributor.authorRandall, J.en
dc.contributor.authorKennedy, N. A.en
dc.contributor.authorLamb, C. A.en
dc.contributor.authorMcCarthy, S.en
dc.contributor.authorAhmad, Tariqen
dc.contributor.authorEdwards, C.en
dc.contributor.authorSerra, E. G.en
dc.contributor.authorHart, A.en
dc.contributor.authorHawkey, C.en
dc.contributor.authorMansfield, J. C.en
dc.contributor.authorMowat, C.en
dc.contributor.authorNewman, W. G.en
dc.contributor.authorNichols, S.en
dc.contributor.authorPollard, M.en
dc.contributor.authorSatsangi, J.en
dc.contributor.authorSimmons, A.en
dc.contributor.authorTremelling, M.en
dc.contributor.authorUhlig, H.en
dc.contributor.authorWilson, D. C.en
dc.contributor.authorLee, J. C.en
dc.contributor.authorPrescott, N. J.en
dc.contributor.authorLees, C. W.en
dc.contributor.authorMathew, C. G.en
dc.contributor.authorParkes, M.en
dc.contributor.authorBarrett, J. C.en
dc.contributor.authorAnderson, C. A.en
dc.date.accessioned2017-01-17T10:17:15Z-
dc.date.available2017-01-17T10:17:15Z-
dc.date.issued2017-01-09-
dc.identifier.citationExploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7. 2017 Feb;49(2):186-192. Epub Jan 9en
dc.identifier.issn1546-1718-
dc.identifier.pmid28067910-
dc.identifier.doi10.1038/ng.3761-
dc.identifier.urihttp://hdl.handle.net/11287/620174-
dc.description.abstractTo further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn's disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve understanding of the biology of complex diseases.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/ng.3761en
dc.rightsArchived with thanks to Nature Geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Gastroenterologyen
dc.titleExploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7.en
dc.typeJournal Articleen
dc.identifier.journalNature Geneticsen
dc.type.versionIn press (epub ahead of print)en

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