rs1010064 (RNU1-146P/TCP1P3): Blood Pressure SNP

Key takeaways

• rs1010064 sits near two pseudogene loci: RNU1-146P (a non-coding copy of a U1 small nuclear RNA gene) and TCP1P3 (a non-coding copy of a t-complex protein gene).
• Blood pressure-associated SNPs from this genomic neighborhood have been used as genetic instruments in Mendelian randomization studies examining whether blood pressure causally affects intraocular pressure.
• Mendelian randomization found no significant causal effect of systolic blood pressure on intraocular pressure (+0.01 mm Hg per 10-mm Hg increase, P > 0.05), despite a much stronger observational association (+0.28 mm Hg).
• No significant causal effect of systolic blood pressure on primary open-angle glaucoma was detected (odds ratio 0.98, 95% CI 0.92 to 1.04).
• Large-scale multi-trait studies have mapped shared genetic architecture between blood pressure traits and Alzheimer's disease, identifying 16 candidate loci with dual associations.

What the research says A Mendelian randomization study used blood pressure-associated SNPs identified from a GWAS of 526,001 European-ancestry participants as genetic instruments to test whether blood pressure causally raises intraocular pressure; the observational association was positive (+0.28 mm Hg corneal-compensated IOP per 10-mm Hg systolic BP), but inverse-variance weighted MR yielded a substantially smaller, non-significant estimate (+0.01 mm Hg), and the authors noted that pleiotropic effects of BP-associated SNPs on IOP may complicate causal interpretation. In a separate multi-trait GWAS, the shared genetic architecture of Alzheimer's disease and cardiovascular traits including blood pressure, coronary artery disease, and atrial fibrillation was examined, identifying 16 genome-wide significant loci with dual associations and highlighting genes in inflammatory signaling pathways (PLEC, C1Q family) as candidate shared mechanisms between heart disease and neurodegeneration.

Reported associations

• Blood pressure: rs1010064 falls in a region with blood pressure GWAS associations identified from a meta-analysis of 526,001 European-ancestry participants; these variants were used to derive genetic instruments for downstream causal analyses.
• Intraocular pressure (Mendelian randomization): In a sample of 70,832 individuals, the estimated causal effect of a 10-mm Hg systolic BP increase on corneal-compensated IOP was +0.01 mm Hg (P > 0.05); for diastolic BP the estimate was +0.13 mm Hg, and for pulse pressure +0.02 mm Hg, neither reaching statistical significance.
• Primary open-angle glaucoma (Mendelian randomization): The causal effect of systolic BP on POAG was odds ratio 0.98 (95% CI 0.92 to 1.04) per 10-mm Hg increase; neither diastolic BP nor pulse pressure showed evidence of a causal effect on this condition.
• Alzheimer's disease and cardiovascular traits (multi-trait GWAS context): A multi-trait GWAS identified 16 loci with genome-wide significant dual associations for AD and cardiovascular traits, implicating inflammatory mechanisms including upregulation of PLEC in left ventricular endothelium and brain astrocytes, and C1Q family gene expression in heart macrophages and brain microglia.

Evidence quality The BP GWAS providing the genetic instruments for this variant's context involved 526,001 European-ancestry participants, giving strong statistical power for SNP discovery. The Mendelian randomization analyses for intraocular pressure and POAG were conducted in a separate, non-overlapping sample of 70,832 individuals, with multiple MR methods applied to assess robustness. The multi-trait AD and cardiovascular GWAS used genome-wide significance thresholds (two-sided P < 5 x 10^-8). Both studies represent large-scale, well-powered analyses. Two caveats apply: the MR analysis explicitly noted that pleiotropic effects of BP-associated SNPs on IOP represent a limitation for causal interpretation, as individual SNPs may affect IOP through pathways independent of blood pressure itself; and both studies focused primarily on European-ancestry populations, limiting generalizability to other groups. Direct functional characterization of the RNU1-146P and TCP1P3 pseudogene loci was not reported in the available studies.

Lifestyle considerations No lifestyle considerations on file for this variant.