Dataset Information

A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

ABSTRACT: Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10-54, per-allele OR = 1.79; and rs9275592, p = 1.14 × 10-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10-10, OR = 1.28; and rs128738, p = 4.60 × 10-9, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.

SUBMITTER: Carmona FD

PROVIDER: S-EPMC5223025 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

Carmona F David FD Vaglio Augusto A Mackie Sarah L SL Hernández-Rodríguez José J Monach Paul A PA Castañeda Santos S Solans Roser R Morado Inmaculada C IC Narváez Javier J Ramentol-Sintas Marc M Pease Colin T CT Dasgupta Bhaskar B Watts Richard R Khalidi Nader N Langford Carol A CA Ytterberg Steven S Boiardi Luigi L Beretta Lorenzo L Govoni Marcello M Emmi Giacomo G Bonatti Francesco F Cimmino Marco A MA Witte Torsten T Neumann Thomas T Holle Julia J Schönau Verena V Sailler Laurent L Papo Thomas T Haroche Julien J Mahr Alfred A Mouthon Luc L Molberg Øyvind Ø Diamantopoulos Andreas P AP Voskuyl Alexandre A Brouwer Elisabeth E Daikeler Thomas T Berger Christoph T CT Molloy Eamonn S ES O'Neill Lorraine L Blockmans Daniel D Lie Benedicte A BA Mclaren Paul P Vyse Timothy J TJ Wijmenga Cisca C Allanore Yannick Y Koeleman Bobby P C BPC Barrett Jennifer H JH Cid María C MC Salvarani Carlo C Merkel Peter A PA Morgan Ann W AW González-Gay Miguel A MA Martín Javier J

American journal of human genetics 20161229 1

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest ...[more]

PMID: 28041642

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Project description:BackgroundFrost is a limiting abiotic stress for the winter pea crop (Pisum sativum L.) and identifying the genetic determinants of frost tolerance is a major issue to breed varieties for cold northern areas. Quantitative trait loci (QTLs) have previously been detected from bi-parental mapping populations, giving an overview of the genome regions governing this trait. The recent development of high-throughput genotyping tools for pea brings the opportunity to undertake genetic association studies in order to capture a higher allelic diversity within large collections of genetic resources as well as to refine the localization of the causal polymorphisms thanks to the high marker density. In this study, a genome-wide association study (GWAS) was performed using a set of 365 pea accessions. Phenotyping was carried out by scoring frost damages in the field and in controlled conditions. The association mapping collection was also genotyped using an Illumina Infinium® BeadChip, which allowed to collect data for 11,366 single nucleotide polymorphism (SNP) markers.ResultsGWAS identified 62 SNPs significantly associated with frost tolerance and distributed over six of the seven pea linkage groups (LGs). These results confirmed 3 QTLs that were already mapped in multiple environments on LG III, V and VI with bi-parental populations. They also allowed to identify one locus, on LG II, which has not been detected yet and two loci, on LGs I and VII, which have formerly been detected in only one environment. Fifty candidate genes corresponding to annotated significant SNPs, or SNPs in strong linkage disequilibrium with the formers, were found to underlie the frost damage (FD)-related loci detected by GWAS. Additionally, the analyses allowed to define favorable haplotypes of markers for the FD-related loci and their corresponding accessions within the association mapping collection.ConclusionsThis study led to identify FD-related loci as well as corresponding favorable haplotypes of markers and representative pea accessions that might to be used in winter pea breeding programs. Among the candidate genes highlighted at the identified FD-related loci, the results also encourage further attention to the presence of C-repeat Binding Factors (CBF) as potential genetic determinants of the frost tolerance locus on LG VI.

Dataset Information

A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

Publications

A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

Similar Datasets

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