rs10016354 (CXCL6): Protein QTL Variant
Key takeaways
- rs10016354 sits near the CXCL6 gene, which encodes a blood-circulating protein studied in large proteomics screens.
- Protein-level genetic variants show about 81.8% consistency between European and Arab populations in cross-population studies.
- Genetic scores for proteins derived from Europeans lose roughly 20% accuracy when applied to Arab populations.
- Ancestry matters when interpreting this variant: cholesterol pathway variants in related studies show 5 to 6 times larger effects in Asians than Europeans.
Key takeaways
- rs10016354 sits near the CXCL6 gene, which encodes a blood-circulating protein studied in large proteomics screens.
- Protein-level genetic variants show about 81.8% consistency between European and Arab populations in cross-population studies.
- Genetic scores for proteins derived from Europeans lose roughly 20% accuracy when applied to Arab populations.
- Ancestry matters when interpreting this variant: cholesterol pathway variants in related studies show 5 to 6 times larger effects in Asians than Europeans.
What the research says A cross-population proteomics study measured 1301 blood-circulating proteins in 2935 Arab participants from the Qatar Biobank and compared genetic associations with those from European cohorts (KORA and INTERVAL), finding that 81.8% of shared protein quantitative trait loci (pQTL) signals colocalized between the two populations, and that European-derived polygenic scores explained approximately one-third of genetic protein heritability in both groups while performing about 20% better in Europeans than in Arabs. A separate metabolome-wide study of 883 plasma metabolites in 8124 Asian adults identified a cholesterol metabolite, 3-beta-hydroxy-5-cholestenoate (3BH5C), whose plasma levels were inversely associated with carotid intima media thickness, a marker of atherosclerosis, with an effect magnitude 5 to 6 times larger in Asians than previously reported in Europeans, and Mendelian randomization supported a causal link between 3BH5C levels and coronary artery disease.
Reported associations
- Cross-population protein quantitative trait loci: A proteomics study of 1301 circulating proteins in an Arab cohort (n=2935) found that 81.8% of pQTL signals shared with European cohorts replicate and colocalize between populations, a result that applies across the full panel of proteins studied including any CXCL6-related signals
- Ancestry effects on polygenic score performance: Polygenic scores for circulating proteins derived from a large European cohort (deCODE) explained approximately one-third of genetic protein heritability in both European and Arab cohorts but performed approximately 20% better in the European cohort
Evidence quality Neither of the available study excerpts reports specific associations, effect sizes, p-values, or replication statistics for rs10016354 or CXCL6 by name. The proteomics pQTL study (Thareja et al., Human Molecular Genetics, 2023) examined 2935 Arab participants and 1301 proteins via SOMAscan but does not identify CXCL6 or rs10016354 as named findings in the available text. The cardiovascular metabolomics study (Sadhu et al., Nature Cardiovascular Research, 2025) examined 8124 Asian adults and 883 metabolites, focusing on FDX1 and cholesterol pathway biology rather than CXCL6. No p-values or variant-specific effect sizes for rs10016354 are available from the provided sources. The evidence base for this specific variant must be considered limited and preliminary based on the available study excerpts.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10016354?
rs10016354 is a genetic variant located near the CXCL6 gene. It falls within a region studied through large-scale proteomics genome-wide association studies that examine how genetic variants influence the levels of circulating proteins in the blood.
What is a protein QTL or pQTL?
A protein quantitative trait locus (pQTL) is a genetic variant associated with measurable differences in the level of a specific protein circulating in the blood. Large studies use platforms like SOMAscan to screen hundreds to thousands of proteins at once and find these associations.
Does this variant work the same way in all populations?
Cross-population proteomics research shows that about 81.8% of shared protein-level genetic signals colocalize between European and Arab populations. However, polygenic scores derived from European cohorts perform roughly 20% less accurately when applied to Arab cohorts.
Is rs10016354 linked to cardiovascular disease?
The available study excerpts do not directly link rs10016354 to cardiovascular outcomes. Related research in Asian populations found that some cholesterol metabolite associations are 5 to 6 times larger in Asians than in Europeans, illustrating that ancestry significantly affects how genetic variants relate to cardiovascular markers.
Why does ancestry matter for interpreting genetic variants?
Polygenic scores and effect sizes can differ substantially across ancestries. Research comparing European and Arab populations shows protein genetic scores lose about 20% accuracy in cross-population applications, meaning variants characterized in one group may behave differently in another.