rs112204826 (CRYAA/LINC00322): Blood Pressure Locus
Key takeaways
- This variant near CRYAA and LINC00322 was identified as a novel blood pressure locus in a study of nearly 100,000 individuals.
- The 75 blood pressure loci from that study together explained about 3% of systolic and diastolic blood pressure variation.
- A polygenic risk score from those loci was associated with time to hypertension onset (hazards ratio 1.18).
- GTEx data shows this variant is associated with increased NDUFV3 gene expression in esophageal tissue.
Key takeaways
- This variant, near CRYAA (Crystallin Alpha A) and LINC00322 (a long intergenic non-coding RNA), was identified as a novel blood pressure locus in a genome-wide study of 99,785 individuals.
- The 75 blood pressure loci from that study together explained about 2.9%, 2.5%, and 3.1% of systolic, diastolic, and pulse pressure variation, respectively.
- A polygenic risk score built from those loci was associated with time to hypertension onset (hazards ratio 1.18).
- GTEx data shows this variant is associated with increased NDUFV3 gene expression in esophageal tissue.
What the research says A genome-wide association study (GWAS, a method that scans genetic variants across the entire genome to find those associated with a trait) of 99,785 individuals in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort identified 75 significant loci (P <= 5 x 10^-8) for blood pressure traits using long-term averaged electronic health record measurements; this locus was among the 39 novel associations reported. Together, all 75 loci explained 2.9%, 2.5%, and 3.1% of variance in systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure, respectively, in non-Hispanic white participants, and using multiple repeated measurements doubled the variance explained compared to a single clinical visit. A polygenic risk score (a numerical score aggregating the effects of many genetic variants) derived from those 75 loci was associated with time to hypertension onset (hazards ratio 1.18, P = 10^-44) in GERA participants. Expression quantitative trait locus (eQTL, an analysis identifying variants that influence how much a gene is expressed) analysis in that study found blood pressure loci as a group were enriched for activity in aorta and tibial artery tissues.
Reported associations
- Systolic blood pressure: Part of a set of 75 loci explaining 2.9% of SBP variance (n=99,785); identified as a novel locus in the GERA blood pressure GWAS.
- Diastolic blood pressure: The same set of loci explained 2.5% of DBP variance in the GERA cohort.
- Pulse pressure: The same set of loci explained 3.1% of pulse pressure variance.
- Hypertension onset (polygenic risk): A risk score from all 75 loci was associated with time to hypertension onset (hazards ratio 1.18, P = 10^-44) in GERA participants.
- NDUFV3 gene expression (esophageal tissue): The alternate allele is associated with increased NDUFV3 expression in esophagus gastroesophageal junction tissue (slope +0.37, p = 4.4e-5, GTEx v11) GTEx Portal.
Evidence quality The blood pressure findings are from the GERA GWAS (n=99,785). Most novel loci were replicated at a Bonferroni-corrected threshold (P <= 0.00067) in combined analyses with the International Consortium for Blood Pressure (ICBP, n=69,396) and UK Biobank (n=152,081). An additional 241 loci emerged in a three-cohort meta-analysis (total n=321,262), though that set lacked a held-out replication sample. Genomic inflation was modest (lambda 1.063 to 1.065, where 1.0 is ideal), indicating limited confounding from population stratification. The 2.9%/2.5%/3.1% variance figures represent aggregate effects across all 75 loci; no per-variant effect size for rs112204826 individually is reported in the available text, which limits interpretation of this locus in isolation. The GTEx eQTL finding (953 donors, FDR < 0.05) is an expression association from an independent dataset and should be treated as mechanistic context rather than a clinical indicator.
Tissue-specific expression effects
- NDUFV3: Carrying the alternate allele is associated with increased NDUFV3 expression (slope +0.37 log2-normalized units) in esophagus gastroesophageal junction tissue GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs112204826?
rs112204826 is a genetic variant located near the CRYAA and LINC00322 genes. It was identified as a novel locus in a blood pressure genome-wide association study of nearly 100,000 individuals.
Is rs112204826 linked to blood pressure?
Yes, this variant falls within a region identified as a novel blood pressure locus in the GERA cohort study (n=99,785). The 75 loci found in that study together explained approximately 3% of systolic and diastolic blood pressure variation, with replication in additional cohorts totaling over 200,000 more participants. No individual effect size for this variant alone is reported.
What gene expression effects does rs112204826 have?
According to GTEx v11 data from 953 donors, carrying the alternate allele is associated with increased expression of the NDUFV3 gene in esophagus gastroesophageal junction tissue.
What is LINC00322?
LINC00322 is a long intergenic non-coding RNA gene, meaning it produces RNA molecules that do not code for proteins. It is part of the genomic region named for this variant alongside CRYAA.
How strong is the evidence for rs112204826 and blood pressure?
The association was discovered in nearly 100,000 individuals and most novel loci were replicated in hundreds of thousands more participants. However, no individual effect size for this specific variant is available in the published excerpts, so its standalone contribution to blood pressure variation remains uncertain.