Sjögren's disease & overlap diseases
From paradox to biology: shared genetic architecture underlies the inverse association between smoking and Sjögren’s disease
Authors' conclusion
The inverse smoking-SjD association likely reflects shared genetic liability rather than a protective causal effect.
Study context
- Population
- Genome-wide association data for smoking initiation and Sjögren's disease (SjD)
- Comparison
- Genetic liability to smoking initiation and SjD risk
- Outcome
- Whether the inverse smoking-SjD association reflects a causal effect of smoking or shared genetic architecture
Methodological detailscross-trait genetic framework, genome-wide causal modelling (CAUSE and latent causal variable analysis), cross-trait pleiotropy analysis, colocalization, proteome-informed mediation analyses
- Cross-trait genetic framework
- Genome-wide causal modelling (CAUSE and latent causal variable analysis)
- Cross-trait pleiotropy analysis
- Colocalization
- Proteome-informed mediation analyses
Main finding
As reported in the abstract
SjD risk per genetic liability to smoking initiation (conventional Mendelian randomization (MR))
Inverse association between genetic liability to smoking initiation and SjD risk, OR
0.53
95% CI 0.34–0.84
Further findings
Shared loci (cross-trait pleiotropy analysis and colocalization)
- Variants identified
- 1536
- Loci
- 11
- Regions with colocalization supporting shared causal variants (3q13.32, 2q22.3, 8p21.2, 14q24.3 and 5q34)
- 5
- Implicated pathways: neuroimmune signalling, epithelial organization, interferon regulation
Proteome-informed mediation
- No circulating proteins robustly mediated the smoking-SjD relationship
Original publication
From paradox to biology: shared genetic architecture underlies the inverse association between smoking and Sjögren’s disease. Rheumatology (Oxford). Published 24 July 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →