Type

Journal Article

Authors

Ross Mcmanus
Richard Jl Anney
Sean Ennis
Dermot Kelleher
Cisca Wijmenga
Gosia Trynka
Clifford Kiat
Valerie Byrnes
Padraic MacMathuna
Colm O'Morain
and 10 others

Subjects

Microbiology

Topics
coeliac disease immune system chronic disease irish population disease susceptibility human genetics intestinal mucosa meta analysis

Common polygenic variation in coeliac disease and confirmation of ZNF335 and NIFA as disease susceptibility loci. (2014)

Abstract Coeliac disease (CD) is a chronic immune-mediated disease triggered by the ingestion of gluten. It has an estimated prevalence of approximately 1% in European populations. Specific HLA-DQA1 and HLA-DQB1 alleles are established coeliac susceptibility genes and are required for the presentation of gliadin to the immune system resulting in damage to the intestinal mucosa. In the largest association analysis of CD to date, 39 non-HLA risk loci were identified, 13 of which were new, in a sample of 12 014 individuals with CD and 12 228 controls using the Immunochip genotyping platform. Including the HLA, this brings the total number of known CD loci to 40. We have replicated this study in an independent Irish CD case-control population of 425 CD and 453 controls using the Immunochip platform. Using a binomial sign test, we show that the direction of the effects of previously described risk alleles were highly correlated with those reported in the Irish population, (P=2.2 × 10(-16)). Using the Polygene Risk Score (PRS) approach, we estimated that up to 35% of the genetic variance could be explained by loci present on the Immunochip (P=9 × 10(-75)). When this is limited to non-HLA loci, we explain a maximum of 4.5% of the genetic variance (P=3.6 × 10(-18)). Finally, we performed a meta-analysis of our data with the previous reports, identifying two further loci harbouring the ZNF335 and NIFA genes which now exceed genome-wide significance, taking the total number of CD susceptibility loci to 42.European Journal of Human Genetics advance online publication, 29 April 2015; doi:10.1038/ejhg.2015.87.
Collections Ireland -> National University of Ireland Galway -> PubMed

Full list of authors on original publication

Ross Mcmanus, Richard Jl Anney, Sean Ennis, Dermot Kelleher, Cisca Wijmenga, Gosia Trynka, Clifford Kiat, Valerie Byrnes, Padraic MacMathuna, Colm O'Morain and 10 others

Experts in our system

1
Ross Mcmanus
Trinity College Dublin
 
2
Richard Anney
Trinity College Dublin
Total Publications: 38
 
3
Sean Ennis
University College Dublin
Total Publications: 52
 
4
Dermot Kelleher
Trinity College Dublin
Total Publications: 144
 
5
Colm O'Morain
Trinity College Dublin
Total Publications: 79