Expressive

rs114676109 (DCDC2): Blood Biomarker Variant

Key takeaways

  • Found in a genome-wide scan of 35 blood and urine biomarkers in over 363,000 UK Biobank participants, replicated in 135,500 Finnish individuals
  • GTEx data shows this variant increases DCDC2 expression in sun-exposed skin
  • The variant also affects expression of MRS2 in four tissue types, GPLD1 in two, and reduces ALDH5A1 expression in liver
  • The source study identified 51 causal biomarker-disease relationships including kidney disease, type 2 diabetes, and gout via Mendelian Randomization

Key takeaways

  • Found in a genome-wide scan of 35 blood and urine biomarkers in over 363,000 UK Biobank participants, with findings replicated in a separate cohort of 135,500 Finnish individuals
  • GTEx data shows this variant increases DCDC2 expression in sun-exposed skin
  • The variant also affects expression of MRS2 in four tissue types, GPLD1 in two, and reduces ALDH5A1 expression in liver
  • The source study identified 51 causal relationships between biomarkers and diseases including kidney disease, type 2 diabetes, gout, and cirrhosis via Mendelian Randomization

What the research says A genome-wide study in the UK Biobank assessed the genetic basis of 35 blood and urine laboratory measurements in 363,228 individuals across five population groups, identifying 1,857 associated loci and 3,374 fine-mapped associations under strict Bonferroni-corrected significance thresholds (p < 5 x 10^-9). Polygenic risk scores built from this study improved genetic risk stratification for chronic kidney disease, type 2 diabetes, gout, and alcoholic cirrhosis when validated in a replication cohort of 135,500 individuals from FinnGen. GTEx v11 data (953 donors, FDR < 0.05) shows rs114676109 acts as an expression quantitative trait locus (eQTL, a variant that influences how much a gene is produced in a given tissue) for four genes across multiple tissue types GTEx Portal.

Reported associations

  • UK Biobank laboratory biomarkers: This variant was included in a genome-wide analysis of 35 blood and urine laboratory measurements in 363,228 UK Biobank participants; available data does not specify which individual biomarker this variant is most strongly associated with
  • DCDC2 expression (eQTL): Increased expression of this gene in sun-exposed lower leg skin GTEx Portal
  • MRS2 expression (eQTL): Increased expression in cultured fibroblasts, adrenal gland, visceral adipose tissue (omentum), and skeletal muscle GTEx Portal
  • GPLD1 expression (eQTL): Increased expression in esophagus muscularis and aorta GTEx Portal
  • ALDH5A1 expression (eQTL): Decreased expression in liver GTEx Portal

Evidence quality The UK Biobank biomarker study is well-powered, drawing on 363,228 discovery participants with replication in 135,500 individuals from FinnGen. Associations were assessed at a strict Bonferroni-corrected threshold of p < 5 x 10^-9 for imputed variants, and LD Score regression intercepts between 0.999 and 1.137 confirm well-controlled population stratification across all 35 biomarker traits. GTEx eQTL associations are derived from 953 donors at FDR < 0.05; the MRS2 eQTL signal is observed across four tissue types, suggesting a relatively broad regulatory effect, while signals for DCDC2, GPLD1, and ALDH5A1 are each confined to one or two tissues, indicating tissue-specific activity. No conflicting findings are present in the available data, though the absence of multiple independent GWAS replications specifically for this variant means its biomarker associations should be treated as preliminary.

Tissue-specific expression effects

  • DCDC2: Increased expression in sun-exposed lower leg skin GTEx Portal
  • MRS2: Increased expression in cultured fibroblasts, adrenal gland, visceral adipose tissue (omentum), and skeletal muscle GTEx Portal
  • GPLD1: Increased expression in esophagus muscularis and aorta GTEx Portal
  • ALDH5A1: Decreased expression in liver GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What gene is rs114676109 associated with?

rs114676109 is labeled as a DCDC2 variant. GTEx data shows the variant increases DCDC2 expression in sun-exposed skin. It also acts as an eQTL (a variant that influences how much a gene is produced) for three other nearby genes, MRS2, GPLD1, and ALDH5A1, each in different tissues.

What blood test is rs114676109 linked to?

This variant was identified in a UK Biobank study examining 35 blood and urine biomarkers in over 363,000 people. The available study data does not name a specific individual biomarker for this variant.

What is an eQTL and why does it matter for rs114676109?

An eQTL (expression quantitative trait locus) is a genetic variant that influences how much a gene is expressed in a given tissue. For rs114676109, GTEx data shows it affects expression of DCDC2, MRS2, GPLD1, and ALDH5A1 across tissues including skin, skeletal muscle, liver, and adrenal gland. These expression effects may hint at biological mechanisms but do not on their own establish clinical outcomes.

How reliable is the evidence for rs114676109?

The primary biomarker study used strict statistical thresholds and involved over 363,000 discovery participants with replication in 135,500 individuals. GTEx eQTL associations come from 953 donors. No additional independent GWAS replications specifically for this variant were available in the reviewed data, so biomarker associations should be considered preliminary.

Is rs114676109 linked to kidney disease or diabetes?

The UK Biobank study in which this variant appears built polygenic models that improved risk stratification for chronic kidney disease and type 2 diabetes, among other conditions. However, those findings involve many variants combined, not rs114676109 alone, and no direct link between this specific variant and those diseases is stated in the available data.