Lupus & antiphospholipid syndrome
A Coding Single‐Nucleotide Polymorphism in β 2 ‐Glycoprotein I ( APOH ) Is Associated With Increased Autoantibody Levels but Reduced Venous Thromboembolism Risk
Authors' conclusion
The APOH genetic signal associated with higher anti-β2GPI levels paradoxically reduced VTE risk, likely mediated by W335S via epitope accessibility and disrupted phospholipid binding.
Study context
- Population
- Participants from the Multi-Ethnic Study of Atherosclerosis (MESA)MESA
- Participants
- 5,969 participants
- Outcome
- Quantitative total anti-β2GPI antibody levels
Methodological detailsmultiancestry, two-sample Mendelian randomization, Bayesian colocalization, fine-mapping, molecular dynamics simulations
- Multiancestry
- Two-sample Mendelian randomization
- Bayesian colocalization
- Fine-mapping
- Molecular dynamics simulations
Main finding
As reported in the abstract
Genome-wide significant association at APOH locus with anti-β2GPI levels (lead SNP rs1801690-G)
- rs1801690-G, β
- 0.21
- P
- P = 1.08 × 10-10
Further findings
Venous thromboembolism (VTE) risk associated with genetically higher anti-β2GPI levels at APOH locus
- β
- −0.25
- P
- P = 3.95 × 10-6
- PP4
- 0.97
- Likely reflecting horizontal pleiotropy rather than a true protective antibody effect
Fine-mapping and functional genomics: most likely causal variant
- Missense variant rs1801690 (W335S) prioritized
Molecular dynamics simulations
- W335S impairs phospholipid binding in domain V while increasing epitope exposure in domains I and II
Original publication
A Coding Single‐Nucleotide Polymorphism in β 2 ‐Glycoprotein I ( APOH ) Is Associated With Increased Autoantibody Levels but Reduced Venous Thromboembolism Risk. Arthritis Rheumatol. Published 7 September 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →