TY - JOUR
T1 - Non-coding DNA in IBD
T2 - From sequence variation in DNA regulatory elements to novel therapeutic potential
AU - Meddens, Claartje Aleid
AU - Van Der List, Amy Catharina Johanna
AU - Nieuwenhuis, Edward Eelco Salomon
AU - Mokry, Michal
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2019.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/5
Y1 - 2019/5
N2 - Genome-wide association studies have identified over 200 loci associated with IBD. We and others have recently shown that, in addition to variants in protein-coding genes, the majority of the associated loci are related to DNA regulatory elements (DREs). These findings add a dimension to the already complex genetic background of IBD. In this review we summarise the existing evidence on the role of DREs in IBD. We discuss how epigenetic research can be used in candidate gene approaches that take non-coding variants into account and can help to pinpoint the essential pathways and cell types in the pathogenesis of IBD. Despite the increased level of genetic complexity, these findings can contribute to novel therapeutic options that target transcription factor binding and enhancer activity. Finally, we summarise the future directions and challenges of this emerging field.
AB - Genome-wide association studies have identified over 200 loci associated with IBD. We and others have recently shown that, in addition to variants in protein-coding genes, the majority of the associated loci are related to DNA regulatory elements (DREs). These findings add a dimension to the already complex genetic background of IBD. In this review we summarise the existing evidence on the role of DREs in IBD. We discuss how epigenetic research can be used in candidate gene approaches that take non-coding variants into account and can help to pinpoint the essential pathways and cell types in the pathogenesis of IBD. Despite the increased level of genetic complexity, these findings can contribute to novel therapeutic options that target transcription factor binding and enhancer activity. Finally, we summarise the future directions and challenges of this emerging field.
KW - gastrointestinal pathology
KW - gene regulation
KW - gene targeting
KW - genetic polymorphisms
KW - Ibd - genetics
UR - http://www.scopus.com/inward/record.url?scp=85060679390&partnerID=8YFLogxK
U2 - 10.1136/gutjnl-2018-317516
DO - 10.1136/gutjnl-2018-317516
M3 - Article
C2 - 30692146
AN - SCOPUS:85060679390
SN - 0017-5749
VL - 68
SP - 928
EP - 941
JO - Gut
JF - Gut
IS - 5
ER -