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Review
. 2020 Nov 1;59(11):3137-3146.
doi: 10.1093/rheumatology/keaa283.

Using functional genomics to advance the understanding of psoriatic arthritis

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Review

Using functional genomics to advance the understanding of psoriatic arthritis

Chenfu Shi et al. Rheumatology (Oxford). .

Abstract

Psoriatic arthritis (PsA) is a complex disease where susceptibility is determined by genetic and environmental risk factors. Clinically, PsA involves inflammation of the joints and the skin, and, if left untreated, results in irreversible joint damage. There is currently no cure and the few treatments available to alleviate symptoms do not work in all patients. Over the past decade, genome-wide association studies (GWAS) have uncovered a large number of disease-associated loci but translating these findings into functional mechanisms and novel targets for therapeutic use is not straightforward. Most variants have been predicted to affect primarily long-range regulatory regions such as enhancers. There is now compelling evidence to support the use of chromatin conformation analysis methods to discover novel genes that can be affected by disease-associated variants. Here, we will review the studies published in the field that have given us a novel understanding of gene regulation in the context of functional genomics and how this relates to the study of PsA and its underlying disease mechanism.

Keywords: GWAS; causal genes; chromatin conformation; functional genomics; genetic susceptibility; psoriatic arthritis; regulation of gene expression.

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Figures

<sc>Fig</sc>. 1
Fig. 1
Using functional genomics to describe GWAS loci (A) A typical GWAS loci usually consists of many variants in high linkage disequilibrium and frequently far away from any genes, which can make the interpretation of the association challenging. (B) It is possible to use a combination of functional genomics techniques to study these loci, such as: chromatin activity to identify which SNPs are functionally relevant and in which cell types; eQTLs to correlate genotype with changes in gene expression; and chromatin conformation to identify regulatory domains that determine which genes can be affected. (C) These methods combined with others allow us to identify the functional importance of GWAS associations in the disease.

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