Journal article

Interactions within the MHC contribute to the genetic architecture of celiac disease

Benjamin Goudey, Gad Abraham, Eder Kikianty, Qiao Wang, Dave Rawlinson, Fan Shi, Izhak Haviv, Linda Stern, Adam Kowalczyk, Michael Inouye



Interaction 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 we..

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Awarded by Australian NHMRC and Heart Foundation

Awarded by NHMRC Peter Doherty Early Career Fellowship

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

MI was supported by a Career Development Fellowship co-funded by the Australian NHMRC and Heart Foundation (#1061435). GA was supported by an NHMRC Peter Doherty Early Career Fellowship (#1090462). MI and GA were also supported by University of Melbourne funding. BG was supported by IBM Research Australia. BG, EK, QW, DR, FS, IH and AK were supported by National ICT Australia (NICTA). The funders provided support in the form of salaries for authors BG, EK, QW, DR, FS, IH and AK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.