rs114161027 (ST3GAL6-AS1): Multi-Tissue eQTL Variant

Key takeaways

• rs114161027 lies near WWP1P1 and ST3GAL6-AS1 and was studied as a protein-level genetic marker across Arab and European populations
• The alternate allele reduces ST3GAL6-AS1 expression in five tissue types including esophagus, adipose, breast, nerve, and colon
• The same allele increases expression of a neighboring gene (ENSG00000286602) in adipose, skin, and nerve tissue
• Genetic protein markers derived from European populations performed approximately 20% less accurately in Arab participants in the cross-population study

What the research says This variant lies in the WWP1P1 - ST3GAL6-AS1 genomic region and was studied in the context of a protein quantitative trait locus (pQTL) genome-wide association study; a pQTL is a genetic variant linked to variation in blood-circulating protein levels. The study compared 2,935 Arab participants from the Qatar Biobank against European cohorts (KORA and INTERVAL), measuring 1,301 proteins using SOMAscan affinity proteomics, and found that 81.8% of shared pQTL signals colocalized across both populations. Tissue-specific expression data show the alternate allele reduces ST3GAL6-AS1 expression in esophagus muscularis, visceral adipose, breast mammary tissue, tibial nerve, and sigmoid colon, while the same allele increases expression of neighboring ENSG00000286602 in subcutaneous adipose, unexposed suprapubic skin, and tibial nerve GTEx Portal.

Reported associations

• Protein quantitative trait locus: rs114161027 was investigated in a cross-population pQTL study of 1,301 proteins in 2,935 Qatar Biobank participants with replication in European cohorts; specific protein associations and effect sizes for this individual variant are not detailed in the available study report
• ST3GAL6-AS1 expression (eQTL): The alternate allele is linked to reduced expression of ST3GAL6-AS1 across five tissue types in GTEx data (953 donors, FDR less than 0.05) GTEx Portal
• ENSG00000286602 expression (eQTL): The alternate allele is linked to increased expression of ENSG00000286602 across three tissue types in GTEx data GTEx Portal

Evidence quality The protein association evidence comes from a large pQTL genome-wide association study using whole-genome sequencing and SOMAscan proteomics in 2,935 Qatar Biobank participants, with replication attempted across European cohorts (KORA and INTERVAL). The study found 81.8% colocalization of shared pQTL signals between populations and reported that protein polygenic scores (PGS) derived from European cohorts performed approximately 20% better in Europeans than in Arabs, a caveat relevant to interpreting variant evidence in Arab and other under-represented populations. The GTEx eQTL data represent findings from 953 donors at FDR less than 0.05, providing directional evidence of this variant's effects on local gene expression across eight distinct tissue-gene combinations. Evidence for specific pQTL protein associations of rs114161027 is preliminary, as no per-variant effect sizes or p-values are reported in the available study text.

Tissue-specific expression effects

• ST3GAL6-AS1: The alternate allele is associated with reduced expression in esophagus muscularis, visceral omentum adipose, breast mammary tissue, tibial nerve, and sigmoid colon GTEx Portal
• ENSG00000286602: The alternate allele is associated with increased expression in subcutaneous adipose, unexposed suprapubic skin, and tibial nerve GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.