ArticleJournal of translational medicine2025
Post-genome-wide association study dissects genetic vulnerability and risk gene expression of Sjögren's disease for cardiovascular disease.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.
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Who cites it
8 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Factors associated with sarcopenia in elderly patients with type 2 diabetes mellitus.Frontiers in endocrinology · 2026Pooled it
- The risk prediction models for sarcopenia in older adults: a systematic review and critical appraisal.Frontiers in public health · 2026Pooled it
- Integrative genomic and spatial transcriptomic analysis elucidates the oligodendrocyte-mediated etiology of epileptic cortical thinning.Epilepsia open · 2026Article
- Integrated post-GWAS, single-cell, and functional analyses prioritizeFrontiers in immunology · 2026Article
- Increased interleukin-8 levels in cord blood serum of newborn-possible effect of cytokine dysregulation in pregnancies complicated by rheumatic disease on newborn vasculature.Frontiers in immunology · 2026Article
- Association between the ratio of uric acid to high-density lipoprotein cholesterol (UHR) and the abnormal risk of sarcopenia: Evidence from two large population-based surveys and interpretable machine learning-driven sarcopenia screening.Therapeutic advances in endocrinology and metabolism · 2026Article
- Enhancing sarcopenia screening in primary care: a machine learning approach using simple physical tests vs. SARC-F in 2,788 community-dwelling older adults.Frontiers in public health · 2026Article
- Sjogren's Disease and Elevated Cardiovascular Risk: Mechanisms and Treatment.Journal of cardiovascular development and disease · 2025Review
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3 authors.
Funding
Abstract
objectivesThis study aims to clarify the genetic associations between Sjögren's Disease (SD) and cardiovascular disease (CVD) outcomes, and to conduct an in-depth exploration of specific pleiotropic susceptibility genes.
methodsWe performed two-sample and multivariable Mendelian randomization (MR) analysis to investigate the association between SD and the risk of ischemic heart disease (IHD) and stroke. Linkage disequilibrium score regression (LDSC) and Bayesian co-localization analyses were employed to assess the genetic associations between traits. Cross-phenotype analyses were employed to identify shared variants and genes, followed by a Transcriptome-Wide Association Study (TWAS) and Multi-marker Analysis of Genomic Annotation (MAGMA) based on Multi-Trait Analysis of GWAS (MTAG) results. To validate the pleiotropic genes, we further analyzed tissue-specific differentially expressed genes (DEGs) related to SD using RNA sequencing data.
resultsThe two-sample and multivariable MR analyses revealed that SD confers a genetic vulnerability to IHD and stroke. LDSC and co-localization analyses indicated a strong genetic linkage between SD and CVDs. Cross-phenotype analyses identified 38 and 37 pleiotropic single nucleotide polymorphisms (SNPs) for SD-Stroke and SD-IHD, respectively, primarily located within the MHC class region on 6p21.32:33 loci. Additionally, TWAS and MAGMA analyses identified pleiotropic genes located outside the MHC regions-seven associated with stroke (UHRF1BP1, SNRPC, BLK, FAM167A, ARHGAP27, C8orf12, and PLEKHM1) and two associated with IHD (UHRF1BP1 and SNRPC). Proxy variants within these genes in SD suggested an increased causal risk for stroke or IHD. Co-localization analysis further reinforced that SD and stroke share significant SNPs within the loci of FAM167A, BLK, C8orf12, SNRPC, and UHRF1BP1. DEG analysis revealed a significant up-regulation of the identified genes in SD-specific tissues.
conclusionsSD appears genetically predisposed to an increased risk of CVDs. Moreover, this research not only identified pleiotropic genes shared between SD and CVDs, but also, for the first time, detected key gene expressions that elevate CVD risk in SD patients-findings that may offer promising therapeutic targets for patient management.
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