rs1023264 (CXCL12): Plasma Protein and Pancreas eQTL

Key takeaways

• rs1023264 sits in the CXCL12 - RPL9P21 genomic region and was identified in a study that screened blood from nearly 11,000 people for genetic links to protein levels
• The alternative allele of this variant links to reduced expression of a nearby gene in pancreatic tissue, based on data from 953 tissue donors
• This variant was found within a proteo-genomic map connecting over 10,000 genetic variants to levels of nearly 4,000 proteins in blood plasma
• No clinical disease associations or lifestyle-related findings are documented for this variant in the available evidence

What the research says A genome-proteome-wide association study profiled 4,775 distinct proteins from blood plasma in 10,708 European-ancestry participants from the Fenland study, identifying 10,674 variant-protein associations across 3,892 proteins; rs1023264 in the CXCL12 - RPL9P21 region was identified within this proteo-genomic framework, which produced a gene-protein-disease map covering 1,859 connections. Across the full study, 64% of novel protein quantitative trait loci (pQTLs, meaning genetic variants linked to protein levels in blood) replicated directionally in independent samples, with cis-pQTLs (variants located near the gene encoding the measured protein) showing 81.2% replication on a complementary antibody-based platform; replication data specific to this locus are not reported in the provided materials. GTEx v11 data from 953 donors shows that the alternative allele at rs1023264 associates with reduced expression of gene ENSG00000303074 in pancreatic tissue (slope -0.35, p=6.6e-8) GTEx Portal.

Reported associations

• Plasma protein level (pQTL): rs1023264 was identified as a genetic variant associated with blood plasma protein levels in a proteo-genomic study of 10,708 European-ancestry participants that profiled 4,775 proteins, using a study-wide significance threshold of p < 1.004 x 10^-11
• Pancreatic gene expression (eQTL): the alternative allele at this locus associates with reduced expression of gene ENSG00000303074 specifically in pancreatic tissue (slope -0.35, p=6.6e-8, FDR (false discovery rate) < 0.05, n=953 donors) GTEx Portal

Evidence quality The proteo-genomic study underlying this variant's identification included 10,708 participants and profiled 4,775 proteins at a strict significance threshold of p < 1.004 x 10^-11. Across the full study, 64% of novel pQTL findings replicated directionally in independent samples, and 81.2% of cis-pQTLs replicated when tested using a complementary antibody-based platform; replication statistics specific to rs1023264 are not available in the provided materials. The GTEx pancreatic eQTL is based on 953 donors at FDR < 0.05, providing reasonable statistical support for the tissue-specific expression finding GTEx Portal. Overall, the evidence base for this locus is limited to discovery-phase proteo-genomic data and reference expression data; no disease outcome associations are documented in the provided studies, and all findings should be treated as preliminary.

Tissue-specific expression effects

• ENSG00000303074: reduced expression in pancreatic tissue is associated with the alternative allele of rs1023264; this eQTL (expression quantitative trait locus, meaning the variant influences how actively this gene is read in that tissue) signal is based on 953 donors at FDR < 0.05 GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.