Late Breaking Abstract - A multi-ancestry meta-analysis offers new insights into the genetics of sarcoidosis, leveraging data from over 2 million individuals across global biobanks and the MESARGEN Consortium

Résumé fourni par la source

Background: Sarcoidosis is an immune-driven condition characterized by non-caseating granulomas in various organs. The disease exhibits heterogeneity, with polygenic traits resulting in different clinical phenotypes, including Löfgren's syndrome (LS) and non-Löfgren's syndrome (nonLS). The genetic framework and allelic variations remain unclear. Methods: We conducted a comprehensive, multi-ancestry genome-wide association study (GWAS) spanning 12 countries, involving a total of 2,244,588 individuals, comprising 19,302 cases and 2,225,286 controls. Deep phenotyping was conducted in seven European cohorts, comprising 825 individuals with LS and 4,021 nonLS cases. The remaining cohorts were characterized primarily using the ICD-10 code system, which accounted for 14,446 cases based on the D86 code. Additionally, we examined human leukocyte antigen (HLA) amino acids within the LS and non-LS groups. To enhance our analysis, we conducted a meta-analysis of the GWAS using an inverse-weighted variance (IVW) model through MR-MEGA software. This process was complemented by gene-based analyses, fine mapping, colocalization, and pathway analyses to gain deeper functional insights. Results: A meta-analysis revealed previously identified loci with more substantial genetic effects marked by regulatory variants, as well as novel loci, such as TRAFD1, C1orf141, and CCDC88B, among others. HLA deep examination revealed significant associations with amino acids in HLA-B, HLA-DRB1, and HLA-DQB1. Conclusion: This study sheds light on novel genomic loci associated with sarcoidosis and clinical phenotypes across ancestries.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.