Expressive

rs10878292 (MSRB3-AS1): PTSD Polygenic Risk

Key takeaways

  • This variant is part of a polygenic risk profile for PTSD that becomes more predictive when combined with a history of childhood trauma (OR = 1.241).
  • Evidence comes from a single small study (68 PTSD cases, 63 controls) and has not been independently replicated.
  • The alternate allele reduces MSRB3 gene expression in the cerebellar hemisphere of the brain.
  • The alternate allele also reduces LEMD3 expression in skeletal muscle.
  • The PTSD findings reflect cumulative polygenic risk across many variants, not the effect of this single variant alone.

Key takeaways

  • This variant is located in MSRB3-AS1 (a locus near the MSRB3 gene) and has been studied as part of a polygenic risk score for post-traumatic stress disorder in women.
  • A polygenic risk score study found that combined genetic susceptibility and childhood trauma significantly increases PTSD likelihood (OR = 1.241, p = 0.03).
  • The alternate allele is associated with reduced MSRB3 expression in the cerebellar hemisphere of the brain.
  • The alternate allele is also associated with reduced LEMD3 expression in skeletal muscle.
  • The PTSD evidence is preliminary, based on a small cohort (68 PTSD cases, 63 controls), and has not been independently replicated.

What the research says A polygenic risk score (PRS) analysis in a Brazilian female cohort of 68 women with PTSD following sexual assault and 63 healthy controls found that genetic liability for PTSD interacts with childhood trauma to increase PTSD risk (OR = 1.241, p = 0.03). The same study identified a further interaction between PRS, traumatic life events, and childhood neglect (OR = 1.010, p = 0.028), with emotional neglect showing a modest independent signal (OR = 1.086, p = 0.014). At the tissue level, the alternate allele at this locus is associated with reduced MSRB3 expression in the cerebellar hemisphere and reduced LEMD3 expression in skeletal muscle GTEx Portal.

Reported associations

  • Post-traumatic stress disorder (polygenic risk interaction with childhood trauma): A PRS study in Brazilian women (n = 68 PTSD, n = 63 controls) found that genetic susceptibility combined with childhood trauma significantly raises PTSD likelihood (OR = 1.241, p = 0.03).
  • PTSD (interaction of polygenic risk with traumatic life events and neglect): PRS, traumatic life events, and childhood neglect together elevated PTSD risk (OR = 1.010, p = 0.028); emotional neglect alone showed a modest signal (OR = 1.086, p = 0.014).
  • MSRB3 expression in brain cerebellar hemisphere: Alternate allele associated with reduced expression (p = 9.5e-5) GTEx Portal.
  • LEMD3 expression in skeletal muscle: Alternate allele associated with reduced expression (p = 2.4e-6) GTEx Portal.

Evidence quality The PTSD association rests on a single small study (68 PTSD cases and 63 controls from a Brazilian female cohort) that has not been replicated in an independent dataset. Critically, the reported effect sizes reflect a composite polygenic risk score rather than the isolated contribution of rs10878292, so the odds ratios cannot be attributed to this variant alone. The study authors note that most prior PTSD GWAS work has focused on European-ancestry male veteran populations, raising uncertainty about generalizability to other groups. The GTEx v11 eQTL evidence (953 donors) is supported by stronger p-values (MSRB3 in cerebellar hemisphere: p = 9.5e-5; LEMD3 in skeletal muscle: p = 2.4e-6), though the biological and clinical significance of these expression differences is not established by the provided data GTEx Portal.

Tissue-specific expression effects

  • MSRB3: The alternate allele is associated with reduced expression in the cerebellar hemisphere of the brain GTEx Portal.
  • LEMD3: The alternate allele is associated with reduced expression in skeletal muscle GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10878292?

rs10878292 is a genetic variant located in the MSRB3-AS1 locus. It has been included in polygenic risk score analyses for PTSD and, based on GTEx tissue expression data, the alternate allele is associated with reduced MSRB3 expression in brain tissue and reduced LEMD3 expression in skeletal muscle.

Is rs10878292 linked to post-traumatic stress disorder?

A polygenic risk score study in Brazilian women found that a genetic risk profile including this variant, combined with childhood trauma, was associated with higher PTSD rates (OR = 1.241, p = 0.03). The evidence is preliminary, drawn from a small cohort of 131 participants, and has not been replicated in other populations.

What does MSRB3-AS1 do?

MSRB3-AS1 is a gene positioned near MSRB3. Based on GTEx expression data, variation at this locus is associated with changes in MSRB3 expression in brain cerebellar tissue and LEMD3 expression in skeletal muscle, though the full functional consequences of those changes remain uncharacterized.

Why does the PTSD association depend on childhood trauma?

The study found that the polygenic risk score for PTSD was more strongly associated with PTSD diagnosis when participants also had a history of childhood trauma, particularly emotional and physical neglect. This gene-environment interaction suggests that genetic liability and early-life stress may jointly influence PTSD risk.

How reliable is the evidence linking rs10878292 to PTSD?

The evidence is early-stage. The single available study enrolled 68 PTSD cases and 63 controls from a Brazilian female cohort and has not been replicated elsewhere. The risk estimate reflects a composite polygenic score across many variants, so this specific SNP's individual contribution to PTSD risk is not established.