Authors
Vinod Kumar, Javier Gutierrez-Achury, Kartiek Kanduri, Rodrigo Almeida, Barbara Hrdlickova, Daria V Zhernakova, Harm-Jan Westra, Juha Karjalainen, Isis Ricano-Ponce, Yang Li, Anna Stachurska, Ettje F Tigchelaar, Wayel H Abdulahad, Harri Lähdesmäki, Marten H Hofker, Alexandra Zhernakova, Lude Franke, Riitta Lahesmaa, Cisca Wijmenga, Sebo Withoff
Publication date
2015/1/15
Journal
Human molecular genetics
Volume
24
Issue
2
Pages
397-409
Publisher
Oxford University Press
Description
Although genome-wide association studies and fine mapping have identified 39 non-HLA loci associated with celiac disease (CD), it is difficult to pinpoint the functional variants and susceptibility genes in these loci. We applied integrative approaches to annotate and prioritize functional single nucleotide polymorphisms (SNPs), genes and pathways affected in CD. CD-associated SNPs were intersected with regulatory elements categorized by the ENCODE project to prioritize functional variants, while results from cis-expression quantitative trait loci (eQTL) mapping in 1469 blood samples were combined with co-expression analyses to prioritize causative genes. To identify the key cell types involved in CD, we performed pathway analysis on RNA-sequencing data from different immune cell populations and on publicly available expression data on non-immune tissues. We discovered that CD SNPs are significantly …
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