Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing

Abstract Deep whole genome sequencing (WGS) allows for the comprehensive study of genetic landscapes at finer resolution than array based methods. We conducted deep WGS on children with the polyarticular form of juvenile idiopathic arthritis (JIA), using 2 independent cohorts to ascertain the sequen...

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Autores principales:	Laiping Wong, Kaiyu Jiang, Yanmin Chen, James N. Jarvis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/965e638a5bbf47e59d5e76bd567ec857
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spelling	oai:doaj.org-article:965e638a5bbf47e59d5e76bd567ec8572021-12-02T15:05:46ZGenetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing10.1038/s41598-017-02966-92045-2322https://doaj.org/article/965e638a5bbf47e59d5e76bd567ec8572017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02966-9https://doaj.org/toc/2045-2322Abstract Deep whole genome sequencing (WGS) allows for the comprehensive study of genetic landscapes at finer resolution than array based methods. We conducted deep WGS on children with the polyarticular form of juvenile idiopathic arthritis (JIA), using 2 independent cohorts to ascertain the sequencing fidelity. Genome wide SNP density analysis identified 18 SNP hotspots with comparison to the 1000 Genome Projects (1KGP) data. A subset of the genes adjacent to SNP hotspots showed statistically significant enrichment in immunological processes. Genes adjacent to indel hotspots were functionally related to G-protein coupled signaling pathways. Further analyses elucidated significantly more JIA SNPs with regulatory potential compared to 1KGP data. Furthermore, SNPs located within linkage disequibilium (LD) blocks containing previously identified JIA-associated SNPs demonstrated higher regulation potential compared to SNPs outside LD blocks. We also demonstrated enrichment of novel JIA variants in histone modification peaks and DNase hypersensitivity sites in B cells. This study greatly expands the number of genetic variants that may contribute to JIA and give us some clues into what may trigger this disease. To date, this study is the first deep WGS effort on children with JIA and provides useful genetic resources for research communities particularly in understanding JIA etiology.Laiping WongKaiyu JiangYanmin ChenJames N. JarvisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laiping Wong Kaiyu Jiang Yanmin Chen James N. Jarvis Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing
description	Abstract Deep whole genome sequencing (WGS) allows for the comprehensive study of genetic landscapes at finer resolution than array based methods. We conducted deep WGS on children with the polyarticular form of juvenile idiopathic arthritis (JIA), using 2 independent cohorts to ascertain the sequencing fidelity. Genome wide SNP density analysis identified 18 SNP hotspots with comparison to the 1000 Genome Projects (1KGP) data. A subset of the genes adjacent to SNP hotspots showed statistically significant enrichment in immunological processes. Genes adjacent to indel hotspots were functionally related to G-protein coupled signaling pathways. Further analyses elucidated significantly more JIA SNPs with regulatory potential compared to 1KGP data. Furthermore, SNPs located within linkage disequibilium (LD) blocks containing previously identified JIA-associated SNPs demonstrated higher regulation potential compared to SNPs outside LD blocks. We also demonstrated enrichment of novel JIA variants in histone modification peaks and DNase hypersensitivity sites in B cells. This study greatly expands the number of genetic variants that may contribute to JIA and give us some clues into what may trigger this disease. To date, this study is the first deep WGS effort on children with JIA and provides useful genetic resources for research communities particularly in understanding JIA etiology.
format	article
author	Laiping Wong Kaiyu Jiang Yanmin Chen James N. Jarvis
author_facet	Laiping Wong Kaiyu Jiang Yanmin Chen James N. Jarvis
author_sort	Laiping Wong
title	Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing
title_short	Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing
title_full	Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing
title_fullStr	Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing
title_full_unstemmed	Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing
title_sort	genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/965e638a5bbf47e59d5e76bd567ec857
work_keys_str_mv	AT laipingwong geneticinsightsintojuvenileidiopathicarthritisderivedfromdeepwholegenomesequencing AT kaiyujiang geneticinsightsintojuvenileidiopathicarthritisderivedfromdeepwholegenomesequencing AT yanminchen geneticinsightsintojuvenileidiopathicarthritisderivedfromdeepwholegenomesequencing AT jamesnjarvis geneticinsightsintojuvenileidiopathicarthritisderivedfromdeepwholegenomesequencing
_version_	1718388719186083840

Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing

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