Expressive

rs117929999 (PRRC2B): Cell-Free DNA and Thrombosis

Key takeaways

  • This variant was studied in relation to plasma cell-free DNA, a heritable blood marker tied to immune-driven blood clotting.
  • Genetic factors explained roughly 26% of variation in cell-free DNA levels in one family-based study.
  • A suggestive but non-significant link between cell-free DNA genetics and thrombosis risk was found in the same cohort.
  • Evidence is preliminary: a single small study with no independent replication.

Key takeaways

  • This variant is located in the PRRC2B gene and has been studied in relation to plasma cell-free DNA (cfDNA), a blood marker linked to immune-driven blood clotting.
  • Plasma cfDNA is heritable: in one family-based study, genetic factors explained roughly 26% of the variation in cfDNA levels (heritability estimate 0.26).
  • NETs (neutrophil extracellular traps, web-like structures released by white blood cells) are the primary source of cfDNA in circulation, and elevated cfDNA has been associated with deep vein thrombosis.
  • Evidence is preliminary, coming from a single small study of Spanish families with unexplained clotting disorders; no independent replication has been reported.

What the research says Plasma cfDNA consists of small double-stranded DNA fragments circulating in the blood and serves as a surrogate marker for NETs, which promote clot formation through a pathway called immunothrombosis. A GWAS in the GAIT-2 cohort of 935 individuals from 35 Spanish families selected for idiopathic thrombophilia (unexplained tendency to form blood clots) found that cfDNA levels are substantially heritable (h2 = 0.26, p = 3.7 x 10^-6). A suggestive but statistically non-significant genetic correlation between cfDNA levels and thrombosis risk was also observed in that cohort (rg = 0.43, p = 0.089).

Reported associations

  • Plasma cell-free DNA levels: The PRRC2B locus, where rs117929999 resides, was identified through a GWAS of plasma cfDNA levels conducted in the GAIT-2 family-based cohort (n = 935 individuals from 35 families).
  • Thrombosis risk (indirect and suggestive): cfDNA levels, which this locus may influence, showed a suggestive genetic correlation with thrombosis susceptibility (rg = 0.43, p = 0.089) in the same cohort; this correlation did not reach conventional statistical significance.

Evidence quality All evidence for this locus comes from a single study using the GAIT-2 cohort, a family-based sample of 935 Spanish individuals from 35 families ascertained through a proband with idiopathic thrombophilia. Because participants were specifically selected for thrombophilia and share familial relatedness, findings may not generalize to unrelated individuals or other ancestries. The heritability estimate for cfDNA (h2 = 0.26) was statistically robust (p = 3.7 x 10^-6), but the genetic correlation with thrombosis was only suggestive (p = 0.089) and did not clear conventional significance thresholds. No replication in an independent cohort was reported for this locus. Overall, the evidence base for rs117929999 specifically is preliminary and should be interpreted with caution.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs117929999 and what gene is it near?

rs117929999 is a genetic variant located in the PRRC2B gene region. It was studied in the context of genome-wide research investigating which genetic variants influence plasma cell-free DNA levels in people with a family history of unexplained blood clotting.

What is cell-free DNA and why does it matter for blood clotting?

Cell-free DNA (cfDNA) consists of small DNA fragments that circulate in the blood. It is released mainly by neutrophils (a type of white blood cell) as part of web-like structures called neutrophil extracellular traps (NETs), which can promote clot formation. Elevated cfDNA levels have been observed in patients with deep vein thrombosis.

Is rs117929999 linked to thrombosis?

Indirectly and tentatively. This locus was identified in a study of cfDNA levels, which showed a suggestive but statistically non-significant genetic correlation with thrombosis risk. No direct association with thrombosis events has been confirmed, and the finding has not been independently replicated.

How heritable are plasma cell-free DNA levels?

In a family-based study of individuals with idiopathic thrombophilia, the heritability of plasma cfDNA was estimated at 0.26, meaning roughly 26% of the variation in cfDNA levels could be attributed to genetic factors.

What is PRRC2B?

PRRC2B, which stands for Proline Rich Coiled-Coil 2B, is a protein-coding gene. Its specific biological role in regulating cell-free DNA or blood clotting has not been fully characterized in the available research.