Immunochip meta-analysis in European and Argentinian populations identifies two novel genetic loci associated with celiac disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-10-07

AUTHORS

Isis Ricaño-Ponce, Javier Gutierrez-Achury, Ana Florencia Costa, Patrick Deelen, Alexander Kurilshikov, Maria Magdalena Zorro, Mathieu Platteel, Adriaan van der Graaf, Serena Sanna, Oscar Daffra, Alexandra Zhernakova, Jingyuan Fu, Gosia Trynka, Edgardo Smecuol, Sonia Isabel Niveloni, Julio Cesar Bai, Vinod Kumar, Cisca Wijmenga

ABSTRACT

Celiac disease (CeD) is a common immune-mediated disease of the small intestine that is triggered by exposure to dietary gluten. While the HLA locus plays a major role in disease susceptibility, 39 non-HLA loci were also identified in a study of 24,269 individuals. We now build on this earlier study by adding 4125 additional Caucasian samples including an Argentinian cohort. In doing so, we not only confirm the previous associations, we also identify two novel independent genome-wide significant associations at loci: 12p13.31 and 22q13.1. By applying a genomics approach and differential expression analysis in CeD intestinal biopsies, we prioritize potential causal genes at these novel loci, including LTBR, CYTH4, and RAC2. Nineteen prioritized causal genes are overlapping known drug targets. Pathway enrichment analysis and expression of these genes in CeD biopsies suggest that they have roles in regulating multiple pathways such as the tumor necrosis factor (TNF) mediated signaling pathway and positive regulation of I-κB kinase/NF-κB signaling. More... »

PAGES

313-323

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  • Journal

    TITLE

    European Journal of Human Genetics

    ISSUE

    3

    VOLUME

    28

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41431-019-0520-4

    DOI

    http://dx.doi.org/10.1038/s41431-019-0520-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1121548611

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31591516


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