rs117983287 (VPS13A): Sepsis 28-Day Mortality Variant

Key takeaways

• rs117983287 is a rare missense variant in the VPS13A gene on chromosome 9q21.2 linked to 28-day death risk after sepsis
• It fell just short of conventional genome-wide significance (p = 8.16 × 10^-8) in a discovery study of 740 sepsis patients
• Independent validation across more than 3,400 additional patients provided supporting evidence (p = 0.03)
• Three loci - VPS13A, CRISPLD2, and a chromosome 13q21.33 region - showed converging evidence for sepsis outcomes across independent datasets
• The biological mechanisms connecting this gene to sepsis survival remain under active investigation

What the research says A genome-wide association study (GWAS) of 740 adult sepsis patients identified rs117983287 - a missense variant (a DNA change that alters a single amino acid in the encoded protein) in the VPS13A (Vacuolar Protein Sorting 13 Homolog A) gene on chromosome 9q21.2 - as the strongest signal for 28-day mortality, achieving p = 8.16 × 10^-8. The association was supported in two independent GWAS cohorts totaling 3,470 patients (p = 0.03) and in an exome sequencing study of 74 patients (p = 0.04). Alongside VPS13A, CRISPLD2 and an intergenic region on chromosome 13q21.33 - previously linked to procalcitonin levels and chronic kidney disease, respectively - also showed converging evidence across independent datasets.

Reported associations

• 28-day mortality after sepsis (discovery): Low-frequency missense variant in VPS13A on chromosome 9q21.2; p = 8.16 × 10^-8 in a GWAS of 740 adult septic patients
• 28-day mortality after sepsis (replication): Supporting signal in additional GWAS cohorts (combined n = 3,470; p = 0.03) and in an independent exome sequencing study (n = 74; p = 0.04)

Evidence quality The discovery GWAS included 740 adult patients, and rs117983287 reached p = 8.16 × 10^-8 - falling just short of the conventional genome-wide significance threshold of 5 × 10^-8. Two independent GWAS cohorts (combined n = 3,470) provided a supporting signal at p = 0.03, and exome sequencing in 74 patients added directional evidence at p = 0.04. No odds ratio was reported specifically for this variant. Total cross-study sample sizes are modest for a GWAS of a critical illness outcome, and the authors explicitly classify all findings as "suggestive," calling for further investigation into VPS13A's underlying biological mechanisms. This evidence should be considered preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.