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Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis
- Source :
- Annals of the Rheumatic Diseases, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, instname, ANNALS OF THE RHEUMATIC DISEASES, r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante, Recercat. Dipósit de la Recerca de Catalunya, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, r-FIHGUV. Repositorio Institucional de Producción Científica de la Fundación de Investigación del Hospital General de Valencia
- Publication Year :
- 2019
- Publisher :
- BMJ Publishing Group, 2019.
-
Abstract
- ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.MethodsWe performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case–control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.ResultsWe identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDRConclusionThese findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.
- Subjects :
- 0301 basic medicine
Oncology
Male
Inflammatory arthritis
Estudio de asociación del genoma completo
Drug repurposing
Genome-wide association study
urologic and male genital diseases
Arthritis, Rheumatoid
Cohort Studies
0302 clinical medicine
Immunology and Allergy
Glycosaminoglycans
glycosaminoglycan
psoriatic arthritis
genome-wide association study
Rheumatoid arthritis
Psoriatic arthritis
Cohort
Female
Signal Transduction
Adult
medicine.medical_specialty
Farmacología
Immunology
N-Acetylglucosaminyltransferases
Polymorphism, Single Nucleotide
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Rheumatology
Internal medicine
Psoriasis
Genetic variation
medicine
Genetics
Humans
Genetic Predisposition to Disease
Genetic association
030203 arthritis & rheumatology
drug repurposing
Artritis
business.industry
Arthritis, Psoriatic
drug repurposing, genetics, genome-wide association study, glycosaminoglycan, psoriatic arthritis
medicine.disease
Genética
genetics
030104 developmental biology
Glycosaminoglycan
Spain
Case-Control Studies
North America
Artritis psoriásica
business
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 14682060 and 00034967
- Database :
- OpenAIRE
- Journal :
- Annals of the Rheumatic Diseases, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, instname, ANNALS OF THE RHEUMATIC DISEASES, r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante, Recercat. Dipósit de la Recerca de Catalunya, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, r-FIHGUV. Repositorio Institucional de Producción Científica de la Fundación de Investigación del Hospital General de Valencia
- Accession number :
- edsair.doi.dedup.....cd564aae447fa9c2ddf988e50d156da3