Sex differences in the genetics of sarcoidosis across European and African ancestry populations

• DOI: 10.3389/fmed.2023.1132799
• Publication Date: 2023-05-12T06:46:15Z
• Authors: Ying Xiong; Susanna Kullberg; Lori Garman; Nathan Pezant; David Ellinghaus; Vasiliki Vasila; Anders Eklund; Benjamin A. Rybicki; Michael C. Iannuzzi; Stefan Schreiber; Joachim Müller-Qu...; Courtney G. Montg...; Johan Grunewald; Leonid Padyukov; Natalia V. Rivera
• Keywords: Genetic Association; Genome-wide Association Study

Background Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations two clinical phenotypes: Löfgren’s syndrome (LS) and non-Löfgren’s (non-LS). Methods A meta-analysis genome-wide association studies was conducted on Europeans African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden ( n = 3,843), Germany 3,342), United States 2,918), followed by an SNP lookup UK Biobank (UKB, 387,945). based Immunochip data consisting 141,000 single nucleotide polymorphisms (SNPs) sex groups. test logistic regression using additive model LS non-LS groups independently. Additionally, gene-based analysis, gene expression, expression quantitative trait loci (eQTL) mapping, pathway analysis were performed discover functionally relevant mechanisms related biological sex. Results We identified Genetic findings explicitly located extended Major Histocompatibility Complex (xMHC). In non-LS, primarily MHC class II subregion ANXA11 . Gene-based eQTL enrichment revealed distinct sex-specific patterns various tissues immune cell types. groups, a map antigen presentation machinery IFN-gamma. maps response lectin-induced complement males maturation migration dendritic cells skin sensitization females identified. Conclusion Our provide new evidence for bias underlying architecture, particularly phenotypes non-LS. Biological likely plays role disease sarcoidosis.