rs115056433 (CLNK): Blood Biomarker Variant

Key takeaways

• rs115056433 is near the CLNK gene and was identified in a major UK Biobank biomarker genetics study
• The study examined 35 blood and urine measurements in over 363,000 people
• 1,857 genetic loci were identified as associated with at least one biomarker
• Results were independently replicated in a Finnish population dataset of 135,500 individuals
• Polygenic risk scores from this study improved genetic risk stratification for diabetes, kidney disease, gout, and cirrhosis

What the research says A genome-wide association study (GWAS, a large-scale scan of DNA variants for statistical links to measured traits) of 35 blood and urine clinical laboratory measurements in 363,228 UK Biobank individuals identified rs115056433, in the CLNK region, as associated with at least one of the measured biomarkers. Across all 35 traits, that study identified 1,857 associated loci and applied fine-mapping - a statistical approach used to narrow down the most likely causal variant within each associated region - yielding 3,374 distinct associations. Polygenic risk scores (models that aggregate many small genetic effects to estimate trait levels) built from the study's findings were validated in FinnGen (n=135,500), where they improved genetic risk stratification for chronic kidney disease, type 2 diabetes, gout, and alcoholic cirrhosis.

Reported associations

• Blood and urine biomarkers (UK Biobank, n=363,228): rs115056433 was one of 1,857 loci reaching genome-wide significance (Bonferroni-corrected p < 5 x 10^-9) across 35 clinical laboratory measurements; the specific biomarker linked to this locus is not specified in the available study text

Evidence quality The primary study was conducted in 363,228 UK Biobank participants from five ancestry groups (White British, non-British White, African, South Asian, and East Asian), with meta-analysis performed across 355,891 individuals. Strict Bonferroni-corrected significance thresholds (p < 5 x 10^-9 for imputed variants) were applied, and fine-mapping was carried out across all identified loci. Findings were independently replicated in FinnGen (n=135,500). LD Score regression - a method for detecting population stratification (systematic genetic differences between ancestry groups that can generate false associations) - showed intercepts between 0.999 and 1.137 across all 35 traits, indicating that confounding from population structure was well controlled. No specific effect size for rs115056433 is reported in the available study text.

Lifestyle considerations No lifestyle considerations on file for this variant.