rs12286616 (NADSYN1): Biomarker and Expression Variant
Key takeaways
- rs12286616 sits near the NADSYN1 gene and was captured in a UK Biobank genome-wide scan of 35 blood and urine biomarkers in 363,228 people
- GTEx tissue data link this variant to reduced NADSYN1 expression in six tissue types: tibial nerve, lung, skin, tibial artery, thyroid, and whole blood
- The same variant is also associated with reduced expression of the nearby DHCR7-DT gene in brain cerebellar hemisphere and heart left ventricle
- These are gene-expression (eQTL) findings - mechanism-level observations, not established clinical outcomes
Key takeaways
- rs12286616 sits near the NADSYN1 gene and was captured in a UK Biobank genome-wide scan of 35 blood and urine biomarkers in 363,228 people
- GTEx tissue data link this variant to reduced NADSYN1 expression in six tissue types: tibial nerve, lung, skin, tibial artery, thyroid, and whole blood
- The same variant is also associated with reduced expression of the nearby DHCR7-DT gene in brain cerebellar hemisphere and heart left ventricle
- These are gene-expression (eQTL) findings - mechanism-level observations, not established clinical outcomes
What the research says
A genome-wide association study (GWAS) of 35 blood and urine biomarkers was conducted in 363,228 UK Biobank participants with meta-analysis across White British, non-British White, African, and South Asian ancestry groups, identifying 1,857 loci containing 3,374 fine-mapped associations with clinical laboratory measurements; the NADSYN1 region was among those captured. Expression quantitative trait loci (eQTL) data from GTEx v11 (953 donors, false discovery rate (FDR) < 0.05) show that the alternate allele at rs12286616 is consistently linked to reduced expression of NADSYN1 across six tissue types GTEx Portal. The same variant is independently associated with reduced expression of the neighboring DHCR7-DT transcript in brain cerebellar hemisphere and heart left ventricle GTEx Portal.
Reported associations
- Blood and urine biomarker locus: rs12286616 falls within a region captured in a large-scale GWAS of 35 clinical laboratory measurements in 363,228 UK Biobank participants (Bonferroni-corrected p < 5 x 10^-9 for common variants); the specific biomarker driving the signal at this locus is not detailed in the provided study excerpt
- NADSYN1 expression (eQTL): The alternate allele is linked to reduced NADSYN1 expression in tibial nerve, lung, skin (non-sun-exposed suprapubic), tibial artery, thyroid, and whole blood GTEx Portal
- DHCR7-DT expression (eQTL): The alternate allele is linked to reduced expression of the DHCR7-DT transcript in brain cerebellar hemisphere and heart left ventricle GTEx Portal
Evidence quality
The UK Biobank biomarker GWAS is one of the largest of its kind, with a primary cohort of 363,228 participants and a meta-analysis spanning 355,891 individuals across multiple ancestry groups. The study applied Bonferroni-corrected significance thresholds (p < 5 x 10^-9 for common imputed variants) and compared effect estimates against 42 previously published cohorts, finding high overall agreement. The GTEx eQTL associations at this locus met a 5% FDR threshold in GTEx v11 across 953 donors, and the direction of effect - reduced expression - is consistent across all six tissue types reported for NADSYN1, suggesting a stable regulatory signal. However, the provided study text does not report the specific effect size or p-value for rs12286616 individually, and independent replication of this specific locus is not documented in the provided sources. The eQTL findings represent evidence of a potential regulatory mechanism, not established clinical associations.
Tissue-specific expression effects
- NADSYN1: Reduced expression in six tissues - tibial nerve, lung, skin (non-sun-exposed suprapubic), tibial artery, thyroid, and whole blood - consistently lower with the alternate allele across all six GTEx Portal
- DHCR7-DT: Reduced expression in brain cerebellar hemisphere and heart left ventricle GTEx Portal
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs12286616?
rs12286616 is a common genetic variant located near the NADSYN1 gene. It was identified in a large UK Biobank genome-wide scan of 35 blood and urine biomarkers and shows consistent gene-expression effects across multiple tissues in GTEx data.
What genes does rs12286616 affect?
GTEx data show rs12286616 is linked to reduced expression of two nearby genes: NADSYN1 in six tissue types (tibial nerve, lung, skin, tibial artery, thyroid, and whole blood), and DHCR7-DT in brain cerebellar hemisphere and heart left ventricle.
What blood or urine biomarker is rs12286616 associated with?
rs12286616 falls in a region identified in a large UK Biobank scan of 35 clinical laboratory measurements across 363,228 participants. The specific biomarker driving the association at this locus is not detailed in the currently available study excerpt.
How reliable is the evidence for rs12286616?
The UK Biobank biomarker study applied strict statistical thresholds (Bonferroni-corrected p < 5 x 10^-9) in a large sample, and the GTEx eQTL findings met a 5% false discovery rate threshold across 953 donors. However, independent replication of this specific locus is not documented in the provided studies.
What does it mean that rs12286616 is an eQTL?
An eQTL (expression quantitative trait locus) is a genetic variant associated with changes in how much a nearby gene is expressed, not necessarily with a clinical disease or trait directly. The eQTL findings for rs12286616 indicate it may influence gene regulation, but this does not on its own establish a clinical effect.