rs111286193 (ZNF628): Aortic Gene Expression Variant

Key takeaways

• rs111286193 sits near the ZNF628 gene (zinc finger protein 628) and was catalogued in one of the largest multi-population genetic studies conducted in the United States, covering over 635,000 veterans.
• The study behind this variant was designed to include participants from European, African, Admixed American, and East Asian backgrounds, directly addressing the historical overrepresentation of European ancestry in genetics research.
• GTEx tissue expression data link this variant to higher activity of two nearby genes, NAT14 and SSC5D, specifically in the wall of the main artery from the heart.
• The specific health trait or disease associated with rs111286193 is not detailed in the available study excerpt, and evidence for disease associations should be considered preliminary.

What the research says The Million Veteran Program (MVP) GWAS - a genome-wide association study (a large-scale scan that identifies genetic variants linked to traits or diseases) - enrolled 635,969 participants across four genetically defined ancestry groups and analyzed associations across 2068 traits, finding 26,049 variant-trait associations; 3477 of these reached statistical significance only after non-European participants were included. Statistical fine-mapping, a method for pinpointing the most likely causal variant within an associated genomic region, identified 57,601 independent signals across 936 traits. Separately, expression quantitative trait locus (eQTL) data from GTEx v11 - a reference dataset derived from 953 tissue donors - show that the alternate allele at rs111286193 is associated with increased expression of NAT14 (N-acetyltransferase 14, a gene involved in protein modification) and SSC5D (scavenger receptor cysteine-rich domain-containing protein, a member of the scavenger receptor family) in aortic artery tissue GTEx Portal.

Reported associations

• NAT14 gene expression (aortic artery): The alternate allele at rs111286193 is associated with increased NAT14 expression in aortic artery tissue, with an effect size slope of +0.80 and p=8.9e-7, based on GTEx v11 analysis of 953 donors GTEx Portal.
• SSC5D gene expression (aortic artery): The alternate allele is also associated with increased SSC5D expression in the same tissue, with an effect size slope of +0.82 and p=8.2e-6 GTEx Portal.

Evidence quality The MVP GWAS (Verma et al., Science 2024) is among the largest multi-population genetic studies conducted to date, with 635,969 participants, more than 44.3 million genotyped variants, and coverage of 2068 traits across four ancestry groups. However, the specific p-value, effect size, and trait associations for rs111286193 from that study are not reported in the available excerpt; the variant is identified contextually as part of this broad effort. The GTEx eQTL associations for NAT14 and SSC5D in aortic artery tissue are based on 953 donors and satisfy a false discovery rate threshold below 0.05, reaching p-values of 8.9e-7 and 8.2e-6 respectively, which are robust by eQTL standards. However, eQTL results describe gene regulatory effects rather than clinical or disease outcomes and should not be interpreted as direct evidence of pathology. No replication in an independent cohort is documented in the provided materials, and no conflicting findings are reported. Overall, evidence for this variant is preliminary and largely mechanistic at this stage.

Tissue-specific expression effects

• NAT14: Increased expression in aortic artery tissue; carriers of the alternate allele at this locus show higher NAT14 (N-acetyltransferase 14) activity in this tissue GTEx Portal.
• SSC5D: Increased expression in aortic artery tissue; the alternate allele is linked to higher SSC5D (scavenger receptor cysteine-rich family protein) levels in the aortic wall GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.