rs114630474 (MSL3B): Blood Biomarker GWAS Variant

Key takeaways

• rs114630474 at the MSL3B locus was identified among 1,857 genetic loci linked to blood or urine biomarkers in a UK Biobank study of 363,228 individuals.
• The study examined 35 clinical laboratory measurements, fine-mapping 3,374 individual variant-trait associations across five ancestry groups.
• The analysis used Mendelian Randomization to identify 51 causal relationships between biomarkers and diseases including gout, stroke, and type 2 diabetes.
• Polygenic risk scores built from this study improved disease risk stratification for chronic kidney disease, type 2 diabetes, gout, and alcoholic cirrhosis in an independent cohort of 135,500 individuals.
• Precise effect size and biomarker-specific data for this variant individually are available in the study's full supplementary tables.

What the research says

A genome-wide association study (GWAS, meaning a large scan of the entire genome for trait-linked variants) of 35 blood and urine biomarkers in UK Biobank (n=363,228) identified 1,857 genetic loci, including a locus designated MSL3B, as associated with at least one clinical laboratory measurement. The study applied Mendelian Randomization (a statistical method that uses genetic variants as natural experiments to estimate causal effects) to discover 51 causal relationships between biomarkers and 40 medically relevant phenotypes, confirming previously known effects such as urate on gout and cystatin C on stroke. Fine-mapping across five ancestry groups yielded 3,374 variant-trait associations, with precise statistics for individual variants documented in the study's supplementary data.

Reported associations

• Blood or urine biomarker (specific trait not detailed in the available study excerpt): rs114630474 at the MSL3B locus was identified as one of 1,857 significantly associated loci in a GWAS of 35 blood and urine biomarkers in UK Biobank (n=363,228). The specific biomarker affected by this variant is documented in the study's full supplementary materials.

Evidence quality

The source study included 363,228 unrelated UK Biobank participants with genome-wide genotyping and imputation using the Haplotype Reference Consortium panel. Meta-analysis was conducted across four ancestry groups: White British (n=318,953), non-British White (n=23,582), African (n=6,019), and South Asian (n=7,338), for a combined meta-analysis sample of 355,891 participants. A Bonferroni-corrected significance threshold of p < 5 x 10^-9 was applied for common variants. Linkage disequilibrium (LD) score intercepts, a diagnostic for population stratification artifacts (meaning false associations driven by ancestry differences rather than biology), ranged from 0.999 to 1.137 across all 35 phenotypes, indicating well-controlled confounding. Heritability attributable to common SNPs (single-nucleotide variants, which are differences at one position in the DNA sequence) ranged from 0.6% for lipoprotein(a) to 23.9% for IGF-1 using LD score regression. Precise p-value, effect size, and replication data for rs114630474 individually are available in the study's supplementary tables and are not reproduced in this entry.

Lifestyle considerations

No lifestyle considerations on file for this variant.