Expressive

rs118156615 (HVCN1): Blood Pressure and Eye Pressure

Key takeaways

  • This blood-pressure-associated variant was used in a Mendelian randomization study of over 526,000 participants to test whether blood pressure causally raises eye pressure.
  • The estimated causal effect of a 10-mm Hg rise in systolic blood pressure on eye pressure was only +0.01 mm Hg, which was not statistically significant.
  • No causal link between blood pressure and primary open-angle glaucoma was found (odds ratio 0.98, 95% CI 0.92-1.04 per 10-mm Hg increase in systolic BP).
  • The apparent observational link between blood pressure and eye pressure appears to reflect confounding rather than a true causal relationship.
  • The variant's alternate allele is linked to increased expression of a nearby gene in multiple brain regions and testis, and to reduced expression of RAD9B in the aorta.

Key takeaways

  • This blood-pressure-associated variant was used in a Mendelian randomization study of over 526,000 participants to test whether blood pressure causally raises eye pressure.
  • The estimated causal effect of a 10-mm Hg rise in systolic blood pressure on eye pressure was only +0.01 mm Hg, which was not statistically significant.
  • No causal link between blood pressure and primary open-angle glaucoma was found (odds ratio 0.98, 95% CI 0.92-1.04 per 10-mm Hg increase in systolic BP).
  • The apparent observational link between blood pressure and eye pressure appears to reflect confounding rather than a true causal relationship.
  • The variant's alternate allele is linked to increased expression of a nearby gene in multiple brain regions and testis, and to reduced expression of RAD9B in the aorta, based on population-level tissue expression data.

What the research says rs118156615, located near the HVCN1 gene, is a blood-pressure-associated single nucleotide polymorphism (SNP - a single-letter variation in the DNA sequence) used as a genetic instrument in a Mendelian randomization (MR) study testing whether blood pressure (BP) causally affects intraocular pressure (IOP - the fluid pressure inside the eye) and primary open-angle glaucoma (POAG - the most common form of glaucoma in people of European ancestry). Mendelian randomization uses genetic variants, which are assigned randomly at conception, to estimate causal effects while avoiding the confounding that plagues observational studies. In a sample of 70,832 individuals with corneal-compensated IOP measurements, MR analysis estimated a causal effect of only +0.01 mm Hg per 10-mm Hg increase in systolic BP (p > 0.05), a negligible change compared with the observational association of +0.28 mm Hg, and for POAG the MR estimate was an odds ratio of 0.98 (95% CI, 0.92-1.04) per 10-mm Hg increase in systolic BP, providing no evidence of a causal effect.

Reported associations

  • Blood pressure: rs118156615 is a blood-pressure-associated SNP identified in a GWAS (genome-wide association study) meta-analysis of 526,001 participants of European ancestry, qualifying it as a genetic instrument for testing downstream effects on eye health outcomes.
  • Intraocular pressure (causal MR estimate): MR analysis in 70,832 individuals found a negligible causal effect of systolic BP on corneal-compensated IOP (+0.01 mm Hg per 10-mm Hg SBP increase; p > 0.05), far smaller than the observational estimate of +0.28 mm Hg. MR estimates for diastolic BP (+0.13 mm Hg) and pulse pressure (+0.02 mm Hg) were also non-significant (both p > 0.05).
  • Primary open-angle glaucoma (causal MR estimate): MR analysis found no significant causal effect of systolic BP on POAG risk (OR = 0.98, 95% CI 0.92-1.04 per 10-mm Hg increase in systolic BP). Diastolic BP and pulse pressure also showed no evidence of a causal effect on this form of glaucoma.

Evidence quality The underlying MR study used BP-associated SNPs from a well-powered GWAS of 526,001 participants and evaluated IOP effects in a distinct non-overlapping sample of 70,832 individuals, which is a recognized methodological strength. However, the authors explicitly flag that some BP-associated SNPs (including variants such as rs118156615) may exert pleiotropic effects on IOP, meaning they could affect eye pressure through pathways other than blood pressure, which would violate a core MR assumption and complicate causal interpretation. None of the MR estimates reached statistical significance, and the authors conclude the causal effect of BP on IOP and POAG is modest at best, or even zero. These are null findings from a single study and should be interpreted cautiously pending independent replication with formal pleiotropy-testing methods.

Tissue-specific expression effects

  • ENSG00000293917: The alternate allele of rs118156615 is associated with increased expression of ENSG00000293917 across seven tissue contexts, covering multiple brain regions including substantia nigra, cerebellum, spinal cord (cervical c-1), cortex, nucleus accumbens (basal ganglia), and putamen (basal ganglia), as well as testis (GTEx v11, 953 donors, FDR < 0.05). GTEx Portal
  • RAD9B: The alternate allele is associated with reduced expression of RAD9B specifically in the aorta (GTEx v11, 953 donors, FDR < 0.05). GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Screening

  • annual blood pressure screening Moderate

    Risk allele A associated with 0.476 mmHg higher diastolic BP in large GWAS (n=526k); eQTL in vascular and neural tissues

Frequently asked questions

What is rs118156615?

rs118156615 is a genetic variant located near the HVCN1 gene. It was identified as a blood-pressure-associated variant in a large genome-wide association study of over 526,000 participants and has been used to investigate whether blood pressure causally affects intraocular pressure and glaucoma risk.

Is rs118156615 linked to glaucoma?

A Mendelian randomization study found no statistically significant causal effect of blood pressure on primary open-angle glaucoma risk (odds ratio 0.98, 95% CI 0.92-1.04 per 10-mm Hg rise in systolic BP). The available evidence does not support a causal link between this blood-pressure variant and glaucoma.

Does blood pressure causally affect eye pressure?

Observational studies show a positive correlation, but Mendelian randomization analysis using genetic instruments like rs118156615 found the causal effect was negligible (+0.01 mm Hg per 10-mm Hg systolic BP increase, not statistically significant). Researchers note that some BP-associated variants may also directly affect eye pressure through other biological pathways, which complicates interpretation.

What is Mendelian randomization and why does it matter here?

Mendelian randomization uses genetic variants, which are assigned randomly at conception, as natural experiments to test causal relationships while reducing bias from confounding. For rs118156615, this method was used to separate any true causal effect of blood pressure on eye pressure from spurious associations driven by shared lifestyle or environmental factors.

What tissues does rs118156615 affect gene expression in?

Population-level tissue expression data from GTEx v11 shows the alternate allele of rs118156615 is associated with increased expression of ENSG00000293917 in multiple brain regions including the substantia nigra, cerebellum, cortex, and basal ganglia structures, as well as in testis. The same allele is linked to reduced expression of RAD9B in the aorta. The functional consequences of these expression changes are not yet established.