rs10033106 (BLOC1S4): Plasma Metabolite GWAS Locus
Key takeaways
- rs10033106 near BLOC1S4/KIAA0232 was one of 31 loci linked to blood metabolite levels in a 2,076-person genome-wide study.
- Genetic factors explained more than 20% of metabolite variation for most of the 217 metabolites studied, outweighing measured clinical factors like age, sex, and BMI.
- The alternate allele is associated with modestly increased SORCS2 gene expression in lung tissue.
- No direct disease associations or lifestyle interactions are documented for this variant in the available evidence.
Key takeaways
- rs10033106 sits near the BLOC1S4 and KIAA0232 genes and was identified as one of 31 loci linked to plasma metabolite levels in a genome-wide study of 2,076 Framingham Heart Study adults.
- In that study, heritable genetic factors explained more than 20% of inter-individual metabolite variation for 66% of the 217 metabolites measured, consistently outweighing measured clinical factors such as age, sex, and BMI.
- The alternate allele of rs10033106 is associated with modestly increased expression of SORCS2 in lung tissue, based on population-level gene expression data from GTEx v11.
- No direct disease associations or lifestyle interactions for this specific variant appear in the available evidence.
What the research says A genome-wide association study (GWAS, meaning a scan of common genetic variants across the entire genome) of 217 plasma metabolites, including more than 100 not measured in prior GWAS, was conducted in 2,076 Framingham Heart Study participants, identifying 31 significant genetic loci, 23 of which had not been previously reported. Estimated heritability (the fraction of inter-individual variation attributable to genetic inheritance) exceeded 20% for 66% of the metabolites assayed, while measured clinical factors accounted for 20% or less of variation in 93% of metabolites. In GTEx v11 expression data from 953 donors, the alternate allele of rs10033106 is associated with increased SORCS2 expression in lung tissue GTEx Portal.
Reported associations
- Plasma metabolite levels: rs10033106, in the BLOC1S4/KIAA0232 locus, was identified as one of 31 genome-wide significant loci in a GWAS of 217 plasma metabolites (including more than 100 not previously measured in GWAS) across 2,076 Framingham Heart Study participants. The specific metabolite associated with this variant is not enumerated in the available study excerpt.
- SORCS2 expression in lung: The alternate allele of rs10033106 is associated with increased SORCS2 expression in lung tissue (slope +0.15 in log2-normalized units, p=1.5x10-5, FDR<0.05), based on cis-eQTL (expression quantitative trait locus, meaning a nearby variant that predicts gene activity levels) mapping in GTEx v11 (953 donors) GTEx Portal.
Evidence quality The metabolomics GWAS was conducted in a single community-based cohort (n=2,076), a modest sample size for this type of research. The platform measured 217 metabolites spanning both polar analytes and lipid analytes using liquid chromatography-mass spectrometry. The specific effect size and p-value for rs10033106 within the GWAS are not provided in the available study excerpt, limiting the precision of conclusions for this particular locus from that source. The GTEx eQTL evidence for SORCS2 in lung is derived from 953 donors in GTEx v11, passing a false discovery rate threshold below 5%; eQTL associations reflect effects on gene activity levels and are not direct measures of clinical outcome GTEx Portal. Overall, the evidence for this variant is preliminary and should be interpreted with caution pending replication in larger, independent datasets.
Tissue-specific expression effects
- SORCS2: The alternate allele of rs10033106 is associated with increased expression of this gene in lung tissue, based on cis-eQTL mapping in GTEx v11. Each additional copy of the alternate allele correlates with modestly higher SORCS2 activity levels. This reflects a gene-expression mechanism finding, not a clinical outcome GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10033106?
rs10033106 is a common genetic variant located near the BLOC1S4 and KIAA0232 genes. It was identified as one of 31 significant loci in a genome-wide scan of 217 plasma metabolites across 2,076 Framingham Heart Study participants.
What is the BLOC1S4 gene?
BLOC1S4 (also catalogued as KIAA0232) is the gene region near rs10033106. The available research identifies this locus as associated with plasma metabolite levels, but the specific metabolite and biological role in this context are not detailed in the available study data.
Is rs10033106 linked to any diseases?
The available research links rs10033106 to plasma metabolite levels and to SORCS2 gene expression in lung tissue. No direct disease association is reported in the available study data for this variant.
What is the connection between rs10033106 and SORCS2?
Population-level gene expression data from GTEx v11 (953 donors) shows that the alternate allele of rs10033106 is associated with modestly higher SORCS2 expression in lung tissue. This is a gene-expression mechanism finding, not a clinical outcome.
How strong is the evidence for rs10033106?
Evidence is preliminary. The metabolomics GWAS covered a single cohort of 2,076 people, a modest sample size for genetic research. The GTEx eQTL finding is based on 953 donors and reflects gene activity levels, not a clinical outcome. Independent replication in larger studies is needed before stronger conclusions can be drawn.