rs10967571 (VLDLR-KCNV2): Cytokine GWAS Locus

Key takeaways

• rs10967571 sits in the genomic region between the VLDLR and KCNV2 genes and was identified in one of the largest cytokine GWAS meta-analyses published to date
• The discovery study spanned 74,783 individuals and combined three independent protein measurement platforms, providing cross-assay validation of detected signals
• Across the broader study, 359 significant variant-cytokine associations were found in 169 independent genomic regions, with this locus among them
• Mendelian randomization in the same study traced cytokine-associated loci to diseases including asthma and Crohn's disease
• The specific cytokine linked to this variant and its individual effect size are not detailed in the available study text

What the research says A genome-wide association study (GWAS) meta-analysis examined 40 circulating cytokines - proteins that coordinate immune responses and serve as potential drug targets - across 74,783 individuals drawn from three independent cohorts, finding 359 significant associations in 169 independent genomic loci, including 150 trans-acting (where a variant influences a gene at a distance) and 19 cis-acting (where a variant influences a nearby gene) associations. The VLDLR-KCNV2 region, where rs10967571 is located, was among the loci identified in this multi-platform discovery effort, which integrated transcriptomic data and Mendelian randomization (a method that uses genetic variants as natural experiments to test causal relationships) to probe regulatory mechanisms and disease links. Within the broader study, drug-target Mendelian randomization using two independent proteomics datasets identified G-CSF/CSF-3 and CXCL9/MIG as potential causal mediators of asthma and Crohn's disease, respectively, and found a potentially protective role for TNF-b in multiple sclerosis.

Reported associations

• Circulating cytokine levels: This variant was identified in a GWAS meta-analysis of 40 circulating cytokines across 74,783 individuals combining Luminex bead-based immunoassay data (N=8,293), Olink proximity extension assay data (N=30,931), and aptamer-based SOMAScan data; the specific cytokine associated with rs10967571 is not named in the available study excerpt
• Immune and inflammatory disease context: The broader study linked cytokine-associated loci to asthma and Crohn's disease through Mendelian randomization, and found evidence of a cytokine network in which TNF-b, VEGF, and IL-1ra exert downstream effects on multiple other cytokines; a direct link from rs10967571 specifically to these conditions is not stated in the available text

Evidence quality The source study meta-analyzed data from 74,783 individuals across three cohorts and three independent proteomic platforms, making it substantially larger than the prior largest targeted cytokine GWAS, which covered up to 8,293 individuals for 41 cytokines. The multi-platform design allows cross-assay reproducibility checks, and the use of Mendelian randomization with colocalization analysis strengthens causal inference for selected cytokine-disease pairs. However, the specific p-value, effect size, and cytokine identity for rs10967571 are not present in the available study excerpt, so the individual evidence strength for this variant cannot be fully evaluated from the provided text alone. The study is framed as a discovery-and-prioritization effort rather than a targeted replication study.

Lifestyle considerations No lifestyle considerations on file for this variant.