Dataset Information

Identification of new risk loci shared across systemic vasculitides points towards potential target genes for drug repurposing.

ABSTRACT:

Objectives

The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap.

Methods

Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta-analysed using ASSET. Pleiotropic variants were functionally annotated and linked to their target genes. Prioritised genes were queried in DrugBank to identify potentially repositionable drugs for the treatment of vasculitis.

Results

Sixteen variants were independently associated with two or more vasculitides, 15 of them representing new shared risk loci. Two of these pleiotropic signals, located close to CTLA4 and CPLX1, emerged as novel genetic risk loci in vasculitis. Most of these polymorphisms appeared to affect vasculitis by regulating gene expression. In this regard, for some of these common signals, potential causal genes were prioritised based on functional annotation, including CTLA4, RNF145, IL12B, IL5, IRF1, IFNGR1, PTK2B, TRIM35, EGR2 and ETS2, each of which has key roles in inflammation. In addition, drug repositioning analysis showed that several drugs, including abatacept and ustekinumab, could be potentially repurposed in the management of the analysed vasculitides.

Conclusions

We identified new shared risk loci with functional impact in vasculitis and pinpointed potential causal genes, some of which could represent promising targets for the treatment of vasculitis.

SUBMITTER: Ortiz-Fernandez L

PROVIDER: S-EPMC10314028 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Identification of new risk loci shared across systemic vasculitides points towards potential target genes for drug repurposing.

Ortiz-Fernández Lourdes L Carmona Elio G EG Kerick Martin M Lyons Paul P Carmona Francisco David FD López Mejías Raquel R Khor Chiea Chuen CC Grayson Peter C PC Tombetti Enrico E Jiang Lindi L Direskeneli Haner H Saruhan-Direskeneli Guher G Callejas-Rubio José-Luis JL Vaglio Augusto A Salvarani Carlo C Hernández-Rodríguez Jose J Cid Maria Cinta MC Morgan Ann W AW Merkel Peter A PA Burgner David D Smith Kenneth Gc KG Gonzalez-Gay Miguel Angel MA Sawalha Amr H AH Martin Javier J Marquez Ana A

Annals of the rheumatic diseases 20230216 6

<h4>Objectives</h4>The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap.<h4>Methods</h4>Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta ...[more]

PMID: 36797040

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Dataset Information

Identification of new risk loci shared across systemic vasculitides points towards potential target genes for drug repurposing.

Objectives

Methods

Results

Conclusions

Publications

Identification of new risk loci shared across systemic vasculitides points towards potential target genes for drug repurposing.

Similar Datasets

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