Expressive

rs11014166 (CACNB2): Diastolic Blood Pressure Variant

Key takeaways

  • The CACNB2 locus is associated with diastolic blood pressure at genome-wide significance, confirmed in studies totaling over 327,000 individuals.
  • This blood pressure locus was first established in a combined analysis of more than 63,000 European-descent individuals.
  • Blood pressure variants including this locus implicate pathways related to cardiometabolic traits and vascular function.
  • Genetic risk scores built from blood pressure loci like this one are associated with coronary disease and myocardial infarction in population studies.
  • All known blood pressure loci together explain only about 2.5% of diastolic blood pressure variation, indicating a small individual effect for each variant.

Key takeaways

  • The CACNB2 locus is associated with diastolic blood pressure at genome-wide significance, confirmed in studies totaling over 327,000 individuals.
  • This blood pressure locus was first established in a combined analysis of more than 63,000 European-descent individuals.
  • Blood pressure variants including this locus implicate pathways related to cardiometabolic traits and vascular function.
  • Genetic risk scores built from blood pressure loci like this one are associated with coronary disease and myocardial infarction in population studies.
  • All known blood pressure loci together explain only about 2.5% of diastolic blood pressure variation, indicating a small individual effect for each variant.

What the research says A large-scale GWAS (genome-wide association study, a method that tests hundreds of thousands of genetic variants across the genome for trait associations) in the CHARGE Consortium (n=29,136, European descent) identified CACNB2, a gene consistently implicated in blood pressure regulation, as one of six loci reaching genome-wide significance (p<5x10-8) for diastolic blood pressure when results were jointly meta-analyzed with the BPgen Consortium (n=34,433). PMID 20173752 A subsequent exome-chip meta-analysis of 327,288 individuals confirmed 39 previously reported blood pressure loci and found that those variants collectively implicate biological pathways related to cardiometabolic traits, vascular function, and development, with genetic risk scores from the identified variants strongly associated with coronary disease and myocardial infarction. PMID 28436984 A GWAS using longitudinal electronic health record data from 99,785 individuals, with replication in combined samples of up to 321,262, found that all identified blood pressure loci together explained approximately 2.9% of systolic, 2.5% of diastolic, and 3.1% of pulse pressure variation, with eQTL (expression quantitative trait locus, meaning a genetic variant linked to differences in gene activity in specific tissues) analysis showing enrichment for blood pressure loci in aorta and tibial artery. PMID 28135244

Reported associations

  • Diastolic blood pressure: One of six loci reaching genome-wide significance (p<5x10-8) in a meta-analysis of the CHARGE (n=29,136) and BPgen (n=34,433) consortia, with CACNB2 specifically named among the genome-wide significant DBP hits. PMID 20173752
  • Diastolic blood pressure (confirmed in independent cohort): Among 39 previously reported blood pressure loci confirmed in a larger exome-chip meta-analysis of 327,288 individuals. PMID 28436984
  • Hypertension onset (aggregate genetic risk): A normalized genetic risk score incorporating blood pressure loci including this region was associated with time-to-onset of hypertension (hazard ratio=1.18, p=10-44) in a study combining up to 321,262 individuals. PMID 28135244

Evidence quality The CACNB2 locus association with diastolic blood pressure was identified at a discovery threshold of p<4x10-7 in the CHARGE Consortium (n=29,136, European descent) and crossed the standard genome-wide significance threshold (p<5x10-8) in joint meta-analysis with BPgen (n=34,433), totaling approximately 63,569 individuals. PMID 20173752 The finding is consistent with replication in a larger exome-chip meta-analysis (n=327,288) that confirmed 39 previously reported blood pressure loci, though the study text provided does not report a specific per-SNP beta coefficient or odds ratio for rs11014166 in that analysis. PMID 28436984 An EHR-based GWAS (n up to 321,262) further corroborates blood pressure associations in this region and notes that using multiple longitudinal measurements doubled the variance explained relative to a single clinical reading. PMID 28135244 Taken together, all known blood pressure loci explain only about 2.5-3.1% of blood pressure variance, indicating that rs11014166, like most GWAS-identified blood pressure variants, contributes a small individual effect. The initial CHARGE discovery relied entirely on European-descent participants; the subsequent larger exome-chip study included multiple ancestries, which somewhat strengthens generalizability.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

Is rs11014166 associated with high blood pressure?

Yes. The CACNB2 locus containing rs11014166 is associated with diastolic blood pressure at genome-wide significance (p<5x10-8), first shown in a combined analysis of approximately 63,000 individuals and confirmed in larger studies of over 320,000 participants.

What is the CACNB2 gene?

CACNB2 is a gene consistently identified in large genome-wide association studies as a blood pressure locus. Multiple independent studies link this region to diastolic blood pressure regulation in population-level research.

How large is the effect of rs11014166 on blood pressure?

The reviewed studies do not report a specific effect size for rs11014166 individually. All identified blood pressure variants combined explain only about 2.5% of diastolic blood pressure variation, indicating that each contributing variant, including this one, has a small effect.

Can blood pressure genetics predict heart disease risk?

Genetic risk scores built from blood pressure variants including loci such as CACNB2 are strongly associated with coronary disease and myocardial infarction in large population studies. These are population-level statistical findings, not individual clinical predictions.

In which tissues might blood pressure variants like rs11014166 act?

Expression QTL analysis across blood pressure loci shows enrichment in aorta and tibial artery tissues, suggesting these variants may influence blood pressure in part through effects in arterial tissue.