Enrichment of Genetic Variants for Rheumatoid Arthritis within T-Cell and NK-Cell Enhancer Regions

Molecular Medicine
Jan FreudenbergWentian Li

Abstract

To identify disease-causative variants, we intersected the published results of a metaanalysis of genome-wide association studies (GWAS) for rheumatoid arthritis (RA) with the set of enhancer regions for 71 primary cell types that was provided by the FANTOM consortium. We first retrieved all single nucleotide polymorphisms (SNPs) that are associated (P < 5 × 10(8)) with RA in the GWAS meta-analysis and that are located in any of these enhancer regions. After excluding the major histocompatibility complex (MHC) region, we identified 50 such RA-associated SNPs that are located in enhancer regions. Enhancer sets from different cell types were then compared with each other for their number of RA-associated SNPs by permutation analysis. This analysis showed that RA-associated SNPs are preferentially located in enhancers from several immunological cell types. In particular, we see a strong relative enrichment in enhancer regions that are active in T cells (P < 0.001) and NK cells (P < 0.001). Several loci display multiple RA-associated SNPs in tight linkage disequilibrium that are located within the same or neighboring enhancers. These haplotypes may have a greater likelihood to influence enhancer activity than any SNP on its own. Ta...Continue Reading

References

Nov 18, 2006·European Journal of Immunology·Lisa StevensJianfei Yang
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium
Sep 7, 2007·The New England Journal of Medicine·Robert M PlengePeter K Gregersen
Sep 17, 2008·Nature Genetics·Anne BartonJane Worthington
May 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lucia A HindorffTeri A Manolio
May 11, 2010·Nature Genetics·Yuta KochiKazuhiko Yamamoto
Oct 4, 2011·American Journal of Human Genetics·Xinli HuSoumya Raychaudhuri
Jan 7, 2014·Nature·Yukinori OkadaRobert M Plenge
Mar 29, 2014·Nature·Robin AnderssonAlbin Sandelin
Jul 25, 2014·Nature·UNKNOWN Schizophrenia Working Group of the Psychiatric Genomics Consortium

❮ Previous
Next ❯

Citations

Nov 5, 2016·Nature Reviews. Rheumatology·Kwangwoo KimSang-Cheol Bae
Jul 1, 2017·Arthritis & Rheumatology·Janneke G C PeetersJorg van Loosdregt
Jul 16, 2020·International Journal of Molecular Sciences·Dmitry S MikhaylenkoAndrey A Zamyatnin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.