Integrative Genetics Analysis of Juvenile Idiopathic Arthritis Identifies Novel Loci
Yun R. Li,
Joseph T Glessner,
Michael E. March,
Jonathan P. Bradfield,
Frank D Mentch,
Debra J. Abrams,
John J Connolly,
Susan D. Thompson,
Carl D. Langefeld,
David N. Glass,
Mara L. Becker,
Benedicte A. Lie,
Debra K. Shivers,
Justine A Ellis,
Jane E. Munro,
Patrick M. Sleiman,
Posted 03 Sep 2020
medRxiv DOI: 10.1101/2020.09.01.20185603
Posted 03 Sep 2020
Juvenile Idiopathic Arthritis (JIA) is the most common type of arthritis among children, encompassing a highly heterogeneous group of immune-mediated joint disorders, being classified into seven subtypes based on clinical presentation. To systematically understand the distinct and shared genetic underpinnings of JIA subtypes, we conducted a heterogeneity-sensitive GWAS encompassing a total of 1245 JIA cases classified into 7 subtypes and 9250 controls. In addition to the MHC locus, we uncovered 16 genome-wide significant loci, among which 15 were shared between at least two JIA subtypes, including 11 novel loci. Functional annotation indicates that candidate genes at these loci are expressed in diverse immune cell types. Further, based on the association results, the 7 JIA subtypes were classified into two groups, reflecting their autoimmune vs autoinflammatory nature. Our results suggest a common genetic mechanism underlying these subtypes in spite of their different clinical disease phenotypes, and that there may be drug repositioning opportunities for rare JIA subtypes.
- Downloaded 501 times
- Download rankings, all-time:
- Site-wide: 75,410
- In allergy and immunology: 160
- Year to date:
- Site-wide: 119,232
- Since beginning of last month:
- Site-wide: 65,430
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!