rs10791821 (MAP3K11): Biomarker Genetics Variant
Key takeaways
- rs10791821 is a variant in the MAP3K11 region studied in a UK Biobank genome-wide scan of 35 clinical biomarkers in 363,228 people
- GTEx data from 953 donors links this variant to increased SNX32 expression in heart, skin, adipose tissue, and nerve
- The same variant is associated with decreased RNASEH2C expression in tibial nerve, skin, and breast tissue
- A GWAS of clinically confirmed gout in Japanese males identified five susceptibility loci with odds ratios up to 1.75, providing pathway context for the metabolic biology surrounding this region
- No lifestyle or clinical guidance can be drawn from current evidence for this specific variant
Key takeaways
- rs10791821 is a variant in the MAP3K11 (mitogen-activated protein kinase kinase kinase 11) region studied in a UK Biobank genome-wide scan of 35 clinical biomarkers in 363,228 people
- GTEx data from 953 donors links this variant to increased SNX32 expression in heart, skin, adipose tissue, and nerve
- The same variant is associated with decreased RNASEH2C expression in tibial nerve, skin, and breast tissue
- A GWAS of clinically confirmed gout in Japanese males identified five susceptibility loci with odds ratios up to 1.75, providing pathway context for the metabolic and uric acid biology surrounding this region
- No lifestyle or clinical guidance can be drawn from current evidence for this specific variant
What the research says
A systematic genome-wide association study (GWAS - a method that scans hundreds of thousands of genetic variants across many individuals to find those statistically linked to a trait) of 35 blood and urine biomarkers in the UK Biobank enrolled 363,228 individuals, identified 1,857 associated loci containing 3,374 fine-mapped associations, and showed that polygenic risk scores built from these biomarkers improved disease risk stratification for gout, chronic kidney disease, type 2 diabetes, and alcoholic cirrhosis in an independent Finnish cohort of 135,500 PMID 33462484. A separate GWAS of clinically confirmed gout (a disease caused by elevated uric acid depositing as crystals in joints) in Japanese males identified five genome-wide significant loci (p<5×10^-8), including urate transporter genes ABCG2 and SLC2A9 and novel loci GCKR (odds ratio [OR - a measure of how much more common a trait is in carriers of one allele versus another] 1.36), MYL2-CUX2 (OR=1.75), and CNIH-2 (OR=1.66), with specific SNPs differentially associated with gout subtypes defined by renal urate handling at r=0.96 PMID 26519597. GTEx v11 additionally identifies rs10791821 as an expression quantitative trait locus (eQTL - a variant that influences transcript levels of a nearby gene in specific tissues) for both SNX32 and RNASEH2C at false discovery rate (FDR) <0.05 across 953 donors GTEx Portal.
Reported associations
- Blood and urine biomarkers (UK Biobank, n=363,228): The chromosomal region containing rs10791821 was among 1,857 loci identified as significantly associated with at least one of 35 clinical laboratory measurements at Bonferroni-corrected p<5×10^-9, with 3,374 total fine-mapped associations across five population groups in meta-analysis PMID 33462484
Evidence quality
The UK Biobank biomarker GWAS PMID 33462484 applied stringent Bonferroni-corrected thresholds (p<5×10^-9) across 9.4 million imputed variants in multi-population meta-analysis (total n=355,891; White British n=318,953), with LD score regression intercepts between 0.999 and 1.137 indicating well-controlled population stratification, and independent validation of derived risk scores in FinnGen (n=135,500). The gout GWAS PMID 26519597 was restricted to clinically confirmed cases - excluding self-reported gout - improving phenotype precision, but was confined to Japanese males, limiting generalizability to other ancestries and to women; it did not directly report an association for rs10791821. The two studies address complementary phenotypes - continuous biomarker quantitative traits versus discrete disease susceptibility - and do not conflict. GTEx v11 eQTL data (953 donors, FDR<0.05) provides mechanistic evidence for tissue-specific expression effects but does not independently establish clinical trait associations; the evidence for this locus overall should be considered preliminary.
Tissue-specific expression effects
- SNX32: The alternative allele of rs10791821 is associated with increased SNX32 expression across five tissues - heart (atrial appendage), non-sun-exposed skin (suprapubic), visceral adipose (omentum), tibial nerve, and esophagus (muscularis); the direction of effect is consistently upward in all five tissues GTEx Portal
- RNASEH2C: The alternative allele is associated with reduced RNASEH2C expression in three tissues - tibial nerve, sun-exposed skin (lower leg), and breast (mammary tissue); the direction of effect is consistently downward across all three GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is MAP3K11?
MAP3K11 (mitogen-activated protein kinase kinase kinase 11) is the gene near which rs10791821 is located. The UK Biobank biomarker study, which examined 35 clinical laboratory measurements in 363,228 people, identified this chromosomal region among its significant loci.
What does rs10791821 do to gene expression?
GTEx v11 data from 953 donors shows that rs10791821 is associated with increased expression of the SNX32 gene in heart, skin, adipose, and nerve tissue, and with decreased expression of RNASEH2C in tibial nerve, skin, and breast tissue. These are mechanistic findings about gene expression levels, not clinical outcomes.
Is rs10791821 linked to gout?
The available studies do not directly link rs10791821 to gout. A GWAS of clinically confirmed gout in Japanese males identified five susceptibility loci including urate transporter genes ABCG2 and SLC2A9, but this SNP was not among the directly reported hits.
What is an eQTL and why does it matter for rs10791821?
An eQTL, or expression quantitative trait locus, is a genetic variant statistically associated with differences in how much a nearby gene is expressed in a given tissue. rs10791821 is an eQTL for both SNX32 and RNASEH2C, meaning carriers of different alleles show measurable differences in transcript levels in multiple tissues, though this does not on its own establish a clinical outcome.
How large were the studies that examined this variant?
The UK Biobank biomarker study included 363,228 individuals, with polygenic risk scores from that study further validated in 135,500 people in the independent FinnGen cohort. The gout GWAS used 945 discovery cases with 1,048 replication cases, all Japanese males with clinically confirmed gout.