rs10458896 (KIF18A): Blood Pressure Variant

Key takeaways

• rs10458896 near the KIF18A gene was identified in a trans-ancestry blood pressure study involving up to 192,000 individuals
• The alternate allele consistently reduces expression of the METTL15 gene across eight tissues in GTEx v11 eQTL data
• Expression reductions are strongest in testis and two brain regions (nucleus accumbens and frontal cortex), with additional effects in peripheral nerve, thyroid, colon, esophagus, and artery
• Blood pressure findings were supported by replication in over 155,000 independent participants
• No per-allele blood pressure effect size for this specific variant is available in the published study text

What the research says A trans-ancestry exome-chip meta-analysis - meaning a combined analysis of participants from European and South Asian backgrounds using a DNA array targeting rare and common coding variants - examined 242,296 variants across up to 192,763 individuals from 51 studies and identified 51 genomic regions reaching genome-wide significance (P less than 5 x 10^-8, a stringent threshold used in large genetic screens to minimize false positives) for at least one blood pressure trait, including 31 novel loci, with findings replicated in 155,063 additional individuals. GTEx v11 data (953 donors, cis-window, FDR less than 0.05) show that the alternate allele at rs10458896 (the KIF18A locus, also an expression-quantitative trait locus, or eQTL, for the neighboring METTL15 gene - meaning the allele is linked to measurable changes in how much METTL15 is expressed in specific tissues) is consistently associated with reduced METTL15 expression across eight tissues GTEx Portal. Specific per-allele blood pressure effect data for this locus are not available in the provided study text.

Reported associations

• Blood pressure and hypertension: this locus was implicated in a trans-ancestry exome-chip study of up to 192,763 individuals covering systolic blood pressure, diastolic blood pressure, pulse pressure, and hypertension; the analysis identified 31 novel associated regions but per-allele effect estimates for this locus are not present in the provided excerpt
• METTL15 gene expression (eQTL): the alternate allele is linked to reduced METTL15 expression in testis, nucleus accumbens (brain), frontal cortex (brain), esophagus muscularis, tibial nerve, sigmoid colon, thyroid, and tibial artery GTEx Portal

Evidence quality The blood pressure evidence derives from a single published trans-ancestry exome-chip meta-analysis (up to 192,763 discovery participants and 155,063 replication participants; 242,296 variants tested; significance threshold P less than 5 x 10^-8). No PMID was provided with this study, limiting bibliographic verification, and per-allele effect estimates for this individual locus are absent from the available text. The GTEx v11 eQTL data (953 donors, cis-window analysis examining variants within a fixed genomic distance of each gene, false discovery rate controlled to limit false positives) show highly significant METTL15 expression reductions across all eight tissues, with p-values ranging from 2.6 x 10^-19 in tibial artery to 1.1 x 10^-24 in testis, providing robust statistical support. eQTL associations are mechanistic observations about gene regulation and do not on their own establish a causal connection to any disease or health outcome.

Tissue-specific expression effects

• METTL15: the alternate allele is linked to reduced expression in testis (strongest effect), nucleus accumbens and frontal cortex (brain), esophagus muscularis, tibial nerve, sigmoid colon, thyroid, and tibial artery (smallest reduction among the eight affected tissues) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.