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dc.contributor.authorGoudey, B
dc.contributor.authorAbraham, G
dc.contributor.authorKikianty, E
dc.contributor.authorWang, Q
dc.contributor.authorRawlinson, D
dc.contributor.authorShi, F
dc.contributor.authorHaviv, I
dc.contributor.authorStern, L
dc.contributor.authorKowalczyk, A
dc.contributor.authorInouye, M
dc.date.accessioned2020-12-22T05:31:24Z
dc.date.available2020-12-22T05:31:24Z
dc.date.issued2017-03-10
dc.identifierpii: PONE-D-16-37547
dc.identifier.citationGoudey, B., Abraham, G., Kikianty, E., Wang, Q., Rawlinson, D., Shi, F., Haviv, I., Stern, L., Kowalczyk, A. & Inouye, M. (2017). Interactions within the MHC contribute to the genetic architecture of celiac disease. PLOS ONE, 12 (3), https://doi.org/10.1371/journal.pone.0172826.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/258306
dc.description.abstractInteraction analysis of GWAS can detect signal that would be ignored by single variant analysis, yet few robust interactions in humans have been detected. Recent work has highlighted interactions in the MHC region between known HLA risk haplotypes for various autoimmune diseases. To better understand the genetic interactions underlying celiac disease (CD), we have conducted exhaustive genome-wide scans for pairwise interactions in five independent CD case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total. We found 14 independent interaction signals within the MHC region that achieved stringent replication criteria across multiple studies and were independent of known CD risk HLA haplotypes. The strongest independent CD interaction signal corresponded to genes in the HLA class III region, in particular PRRC2A and GPANK1/C6orf47, which are known to contain variants for non-Hodgkin's lymphoma and early menopause, co-morbidities of celiac disease. Replicable evidence for statistical interaction outside the MHC was not observed. Both within and between European populations, we observed striking consistency of two-locus models and model distribution. Within the UK population, models of CD based on both interactions and additive single-SNP effects increased explained CD variance by approximately 1% over those of single SNPs. The interactions signal detected across the five cohorts indicates the presence of novel associations in the MHC region that cannot be detected using additive models. Our findings have implications for the determination of genetic architecture and, by extension, the use of human genetics for validation of therapeutic targets.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleInteractions within the MHC contribute to the genetic architecture of celiac disease
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0172826
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentComputing and Information Systems
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.affiliation.departmentChancellery Research
melbourne.source.titlePLoS One
melbourne.source.volume12
melbourne.source.issue3
melbourne.identifier.nhmrc1061435
melbourne.identifier.nhmrc1090462
dc.rights.licenseCC BY
melbourne.elementsid1191054
melbourne.contributor.authorAbraham, Gad
melbourne.contributor.authorStern, Linda
melbourne.contributor.authorInouye, Michael
melbourne.contributor.authorWang, Qiao
melbourne.contributor.authorKowalczyk, Adam
melbourne.contributor.authorGoudey, Benjamin
melbourne.contributor.authorRAWLINSON, DAVID
melbourne.contributor.authorSHI, FAN
dc.identifier.eissn1932-6203
melbourne.identifier.fundernameidNHMRC, 1061435
melbourne.identifier.fundernameidNHMRC, 1090462
melbourne.accessrightsOpen Access


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