The quest for genetic risk factors for Crohn's disease in the post-GWAS era

Karin Fransen, Mitja Mitrovic, Cleo C. Van Diemen, Rinse K. Weersma*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)
94 Downloads (Pure)

Abstract

Multiple genome-wide association studies (GWASs) and two large scale meta-analyses have been performed for Crohn's disease and have identified 71 susceptibility loci. These findings have contributed greatly to our current understanding of the disease pathogenesis. Yet, these loci only explain approximately 23% of the disease heritability. One of the future challenges in this post-GWAS era is to identify potential sources of the remaining heritability. Such sources may include common variants with limited effect size, rare variants with higher effect sizes, structural variations, or even more complicated mechanisms such as epistatic, gene-environment and epigenetic interactions. Here, we outline potential sources of this hidden heritability, focusing on Crohn's disease and the currently available data. We also discuss future strategies to determine more about the heritability; these strategies include expanding current GWAS, fine-mapping, whole genome sequencing or exome sequencing, and using family-based approaches. Despite the current limitations, such strategies may help to transfer research achievements into clinical practice and guide the improvement of preventive and therapeutic measures.

Original languageEnglish
Article number13
Number of pages10
JournalGenome medicine
Volume3
DOIs
Publication statusPublished - 2011

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