Objective: Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants.
Methods: Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing.
Results: More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously.
Conclusion: Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/art.39275 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Serum bactericidal activity against meningococcus in patients with systemic lupus erythematosus.
Clin Exp Pediatr
January 2025
Department of Pediatrics, Hallym University Sacred Heart Hospital, Anyang, Korea.
Background: Patients with systemic lupus erythematosus (SLE) are susceptible to infectious diseases owing to various immunosuppressive treatments and disease characteristics. Meningococcal infections progress rapidly with a high incidence of severe complications and mortality; therefore, meningococcal vaccination is needed. However, there is limited evidence regarding the immunity and immunogenicity of patients with SLE.
View Article and Find Full Text PDFMaternal and fetal outcomes in Latin American SLE pregnancies: A systematic review and meta-analysis.
Autoimmun Rev
January 2025
Rheumatologist, Research Professor - Research Institute Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá 111411, Colombia. Electronic address:
Introduction: Systemic lupus erythematosus (SLE) predominantly affects women, especially during their reproductive years, leading to increased risks during pregnancy. Latina women develop SLE at a younger age, which increases their susceptibility to pregnancy complications such as pre-eclampsia, preterm birth and fetal growth restriction.
Objective: The purpose of this study is to systematically review maternal and fetal outcomes in pregnant Latina women with SLE and to perform a meta-analysis to assess specific risks associated with the disease.
Defining Mechanistic Links Between the Non-Coding Variant rs17673553 in and Lupus Susceptibility.
Int J Mol Sci
January 2025
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by widespread inflammation and autoantibody production. Its development and progression involve genetic, epigenetic, and environmental factors. Although genome-wide association studies (GWAS) have repeatedly identified a susceptibility signal at 16p13, its fine-scale source and its functional and mechanistic role in SLE remain unclear.
View Article and Find Full Text PDFCausal relationship between rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and risk of prostate cancer: Multivariable and bidirectional Mendelian-randomization analyses.
Medicine (Baltimore)
January 2025
Department of Urology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China.
Previous studies have suggested an association between autoimmune diseases (AIDs) and the risk of prostate cancer (PCa). However, the causal relationship between AID and PCa remained unclear. The purpose of this study was to investigate the causal association between 3 common AIDs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS), and the risk of PCa.
View Article and Find Full Text PDFGenetic Commonalities Between Metabolic Syndrome and Rheumatic Diseases Through Disease Interactome Modules.
J Cell Mol Med
January 2025
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
This study aims to elucidate the potential genetic commonalities between metabolic syndrome (MetS) and rheumatic diseases through a disease interactome network, according to publicly available large-scale genome-wide association studies (GWAS). The analysis included linkage disequilibrium score regression analysis, cross trait meta-analysis and colocalisation analysis to identify common genetic overlap. Using modular partitioning, the network-based association between the two disease proteins in the protein-protein interaction set was divided and quantified.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!