Expressive

rs117605916 (ALDH16A1): Blood Biomarker Variant

Key takeaways

  • rs117605916 in ALDH16A1 was flagged in a genome-wide study of 35 blood and urine biomarkers covering 363,228 UK Biobank participants.
  • The alternate allele increases PRR12 gene activity in thyroid, liver, esophagus, pituitary, pancreas, and skin.
  • The same allele reduces PIH1D1 gene activity specifically in testis.
  • Replication findings come from an independent Finnish cohort of 135,500 individuals (FinnGen).
  • No lifestyle-specific effects for this variant have been documented in the available studies.

Key takeaways

  • rs117605916 in ALDH16A1 was flagged in a genome-wide study of 35 blood and urine biomarkers covering 363,228 UK Biobank participants.
  • The alternate allele increases PRR12 gene activity in thyroid, liver, esophagus, pituitary, pancreas, and skin.
  • The same allele reduces PIH1D1 gene activity specifically in testis.
  • Replication findings come from an independent Finnish cohort of 135,500 individuals (FinnGen).
  • No lifestyle-specific effects for this variant have been documented in the available studies.

What the research says A genome-wide association study of 35 blood and urine biomarkers in 363,228 UK Biobank participants identified 1,857 loci with 3,374 fine-mapped associations, with rs117605916 in ALDH16A1 (aldehyde dehydrogenase 16 family member A1) among those findings PMID 33462484. The study applied stringent Bonferroni-corrected significance thresholds (p < 5 x 10^-9 for imputed variants) and used Mendelian Randomization to uncover 51 causal relationships among the 35 biomarkers, including urate's causal effect on gout PMID 33462484. GTEx v11 data from 953 donors shows the alternate allele at this locus acts as an expression quantitative trait locus (eQTL, a variant that influences how much a nearby gene is produced) for PRR12 across seven tissues and for PIH1D1 in testis GTEx Portal.

Reported associations

  • Blood and urine biomarkers (UK Biobank): rs117605916 was identified as a significant locus in a scan of 35 blood and urine biomarkers in 363,228 participants; the panel included biomarkers spanning lipids, kidney function, liver enzymes, and metabolic markers including urate PMID 33462484.
  • PRR12 gene expression in thyroid: The alternate allele is linked to increased PRR12 expression in thyroid tissue (p=2.1e-36) GTEx Portal.
  • PRR12 gene expression in multiple other tissues: Increased PRR12 expression is also observed in esophagus mucosa (p=1.0e-25), sun-exposed skin (p=2.0e-23), non-sun-exposed skin (p=7.0e-18), pituitary (p=1.8e-9), pancreas (p=1.4e-9), and liver (p=3.5e-8) GTEx Portal.
  • PIH1D1 gene expression in testis: The alternate allele is linked to reduced PIH1D1 expression in testis (p=2.1e-7) GTEx Portal.

Evidence quality The UK Biobank biomarker GWAS used a discovery cohort of 363,228 participants across five population groups (White British n=318,953; non-British White n=23,582; African n=6,019; South Asian n=7,338; East Asian n=1,082), followed by meta-analysis, and validated polygenic risk models in FinnGen (n=135,500) PMID 33462484. Linkage disequilibrium score intercepts between 0.999 and 1.137 across the 35 phenotypes indicate population stratification was well controlled PMID 33462484. The GTEx PRR12 signals in thyroid (p=2.1e-36) and esophagus mucosa (p=1.0e-25) are among the strongest eQTL associations in the dataset; the PIH1D1 testis signal sits at a more modest significance level (p=2.1e-7, FDR<0.05), reflecting the smaller testis donor sample in GTEx GTEx Portal. The available study excerpt does not detail which specific biomarker is most strongly associated with this locus, and per-biomarker effect sizes for rs117605916 are not provided in the available text.

Tissue-specific expression effects

  • PRR12: The alternate allele is linked to increased expression across seven tissues (thyroid, esophagus mucosa, liver, pituitary, pancreas, non-sun-exposed skin, and sun-exposed skin), with the strongest signal in thyroid GTEx Portal.
  • PIH1D1: The alternate allele is linked to reduced expression specifically in testis GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the ALDH16A1 gene?

ALDH16A1 stands for aldehyde dehydrogenase 16 family member A1, a member of the aldehyde dehydrogenase enzyme family. rs117605916 is a genetic variant within this gene, identified in a large UK Biobank study of blood and urine biomarkers.

What blood or urine biomarkers is rs117605916 linked to?

rs117605916 was identified as a significant locus in a UK Biobank study of 35 blood and urine biomarkers in 363,228 individuals. The panel included markers spanning lipids, kidney function, liver enzymes, and metabolic measurements including urate, though the available study text does not specify which biomarker is most strongly tied to this variant.

What does rs117605916 do to gene expression?

GTEx data from 953 donors shows the alternate allele increases expression of the PRR12 gene in seven tissues including thyroid, liver, esophagus mucosa, pituitary, pancreas, and both sun-exposed and non-sun-exposed skin. The same allele reduces PIH1D1 gene expression in testis.

Is rs117605916 associated with gout or urate?

The UK Biobank biomarker study that identified this locus included urate among its 35 measured biomarkers and reported a causal relationship between urate and gout in its overall Mendelian Randomization findings. The available study text does not explicitly state whether this variant is specifically associated with urate levels.

How large was the study that identified rs117605916?

The discovery cohort included 363,228 UK Biobank participants across five population groups. Polygenic risk models built from these findings were validated in an independent Finnish cohort of 135,500 individuals (FinnGen).