rs11693502 (DARS1-AS1): Artery and Nerve eQTL Variant

Key takeaways

• The alternate allele at rs11693502 is associated with increased DARS1-AS1 expression in aortic artery, tibial artery, tibial nerve, and unexposed skin
• The same allele is linked to reduced MCM6 expression in aortic artery, tibial artery, esophageal muscularis, and thyroid
• This variant was genotyped in the VA Million Veteran Program, one of the largest and most diverse US genomic studies, with 635,969 participants (29% non-European ancestry)
• No specific clinical trait associations for this variant are described in available study summaries; current evidence is limited to tissue-specific gene expression effects

What the research says The VA Million Veteran Program (MVP), a longitudinal genomic cohort of 635,969 US Veterans including 29% from non-European ancestries, performed genome-wide association studies (GWASs, systematic surveys of genetic variants across the full genome) across 2068 traits and identified 26,049 variant-trait associations with fine-mapping (statistical narrowing to the most likely causal variants) of 57,601 independent signals, though specific associations for rs11693502 are not described in the available summaries. GTEx v11 expression data from 953 donors show that the alternate allele at this locus is associated with increased expression of DARS1-AS1 in aortic artery (effect size +0.36 in log2-normalized units, a scale where positive values indicate greater gene activity), tibial artery (+0.36), tibial nerve (+0.35), and unexposed suprapubic skin (+0.26), with all associations at p < 4e-12 GTEx Portal. The same allele is associated with reduced expression of MCM6 in aortic artery (-0.33), tibial artery (-0.29), esophageal muscularis (-0.28), and thyroid (-0.25), all at p < 6e-15 GTEx Portal.

Reported associations

• DARS1-AS1 expression: The alternate allele is associated with increased DARS1-AS1 expression in aortic artery (effect size +0.36, p = 1.1e-12), tibial artery (+0.36, p = 2.3e-15), tibial nerve (+0.35, p = 1.9e-13), and unexposed suprapubic skin (+0.26, p = 3.5e-12); effect sizes are in log2-normalized units GTEx Portal
• MCM6 expression: The alternate allele is associated with reduced MCM6 expression in aortic artery (effect size -0.33, p = 5.2e-15), tibial artery (-0.29, p = 3.0e-15), esophageal muscularis (-0.28, p = 9.2e-16), and thyroid (-0.25, p = 1.8e-17); effect sizes are in log2-normalized units GTEx Portal

Evidence quality The tissue expression data come from GTEx v11, based on 953 donors using a false discovery rate (FDR, a statistical correction that limits false positives across many simultaneous tests) threshold below 0.05 for all reported signals. P-values across all eight tissue-gene associations range from 1.1e-12 to 1.8e-17, indicating strong statistical confidence in each expression signal. The MVP GWAS that genotyped this variant is large in scale and notable for its population diversity, but the specific contribution of rs11693502 to any phenotype (observable trait or condition) in that study is not described in the available text. No conflicting results appear across the available sources. The evidence here is molecular and should be considered preliminary with respect to any clinical or health interpretation: eQTL associations describe gene activity patterns in tissue samples, and no downstream biological or medical consequences are characterized in the provided sources.

Tissue-specific expression effects

• DARS1-AS1 (ENSG00000308748): Increased expression in aortic artery, tibial artery, tibial nerve, and unexposed suprapubic skin; the strongest effects appear in arterial and nerve tissues GTEx Portal
• MCM6: Reduced expression in aortic artery, tibial artery, esophageal muscularis, and thyroid; the largest reduction is observed in aortic artery GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.