Expressive

rs10821808 (ANK3): Systolic Blood Pressure Variant

Key takeaways

  • rs10821808 near ANK3 is associated with about 0.29 mm Hg lower systolic blood pressure per copy of the A allele
  • The finding met genome-wide significance standards and was replicated in nearly 290,000 East Asian and European participants
  • The association was discovered primarily in East Asians and confirmed across ethnicities, suggesting broad relevance
  • GTEx data link this variant to increased expression of ANK3-DT in ovary and thyroid, and increased ANK3 expression in esophageal tissue
  • The per-allele blood pressure effect is modest, consistent with most common genetic variants found in large GWAS

Key takeaways

  • rs10821808, a common genetic variant near the ANK3 gene on chromosome 10, is associated with modestly lower systolic blood pressure (the peak pressure in arteries when the heart beats).
  • Each copy of the A allele is linked to approximately a 0.29 mm Hg decrease in systolic blood pressure, an effect that met the genome-wide significance threshold (p = 3.4 x 10^-9) and was replicated.
  • The finding comes from a large multi-ethnic study of nearly 290,000 East Asian and European participants, adding confidence to its relevance across ancestries.
  • GTEx data show this variant is also associated with increased expression of ANK3-DT (a divergent transcript near ANK3) in ovary and thyroid tissue, and increased ANK3 expression in esophageal tissue.
  • The absolute blood pressure effect per allele is small, consistent with common blood pressure variants identified by genome-wide association studies.

What the research says A multi-stage genome-wide association study (GWAS - a scan of nearly the entire genome to identify genetic variants linked to a trait) conducted principally in East Asians, with follow-up meta-analysis including Europeans (up to N = 288,917 total), identified rs10821808 near the ANK3 locus on chromosome 10 as a systolic blood pressure locus PMID 31601843. The A allele (effect allele frequency approximately 0.58, making it the more common allele) was associated with a -0.29 mm Hg change in systolic blood pressure per allele copy (standard error 0.05, p = 3.4 x 10^-9), and the association was genome-wide significant and replicated within the same study PMID 31601843.

Reported associations

  • Systolic blood pressure: Each additional A allele associated with approximately -0.29 mm Hg (SE 0.05, p = 3.4 x 10^-9, N = 288,917, East Asian and European populations combined, genome-wide significant and replicated) PMID 31601843

Evidence quality The blood pressure association for rs10821808 rests on a multi-stage GWAS with a discovery cohort of 130,777 East Asians and a follow-up meta-analysis with Europeans, for a combined N of 288,917 PMID 31601843. The p-value of 3.4 x 10^-9 clears the conventional genome-wide significance threshold (p < 5 x 10^-8), and the study explicitly categorizes this finding as replicated. Multi-ethnic GWAS efforts such as a cross-population atlas covering 220 phenotypes in BioBank Japan (n = 179,000) combined with UK Biobank and FinnGen have broadened the resolution of blood pressure genetics in non-European populations PMID 34385711. No conflicting findings are reported for this variant across the provided studies. The per-allele effect size (-0.29 mm Hg on systolic blood pressure) is modest, as is typical for common blood pressure variants found by GWAS.

Tissue-specific expression effects

  • ANK3-DT (a divergent transcript near the ANK3 gene): this variant is associated with increased expression in ovary, thyroid, and non-sun-exposed suprapubic skin GTEx Portal
  • ANK3: this variant is associated with increased expression in esophageal mucosa and esophageal muscularis GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10821808?

rs10821808 is a common genetic variant (a single nucleotide polymorphism, or SNP - a single-letter difference in DNA sequence) located near the ANK3 gene on chromosome 10. Large genetic studies have linked it to small but statistically robust differences in systolic blood pressure.

Is rs10821808 associated with high blood pressure?

Studies find that people carrying more copies of the A allele at rs10821808 tend to have slightly lower systolic blood pressure on average. The effect is small - about 0.29 mm Hg per allele copy - and this variant is one of many genetic factors that collectively influence blood pressure.

Which populations were studied for rs10821808?

The primary discovery GWAS was conducted in 130,777 East Asian individuals, with follow-up meta-analysis including Europeans, for a combined sample of nearly 290,000 participants. The association was genome-wide significant and replicated across this multi-ethnic study.

What tissues show expression changes linked to rs10821808?

GTEx data show that rs10821808 is associated with increased expression of ANK3-DT in ovary, thyroid, and non-sun-exposed skin, and with increased ANK3 expression in esophageal mucosa and muscularis. These are gene-expression findings and do not directly imply clinical outcomes.

How strong is the evidence linking rs10821808 to blood pressure?

The evidence is considered strong by genetic epidemiology standards: the association passed the genome-wide significance threshold (p = 3.4 x 10^-9), was replicated, and was based on a combined sample of nearly 290,000 participants across two ethnic groups. The per-allele effect size is modest.