Diastolic Blood Pressure and Your Genetics
Written by Scott Peeples, BS Biomedical Sciences · ExomeDNA Founder
Research base: Robust.
Maximum diastolic blood pressure — the highest reading recorded across multiple clinic visits, transformed to a normal distribution for statistical analysis — captures peak arterial load. Verma et al. (2024) identified 112 associated genes for this phenotype in a large multi-ancestry GWAS, the richest gene set for a diastolic BP phenotype in this series. The top signals include FGF5, BANK1, CCDC141, TET2, and ANAPC4, spanning vascular growth factor signaling, immune scaffolding, cardiac development, and epigenetic regulation.
What is diastolic blood pressure?
Diastolic blood pressure is the pressure in arteries during the cardiac resting phase between beats. Persistent elevation above 80 mmHg damages arterial walls and increases long-term cardiovascular burden. The maximum phenotype captures the single highest reading across multiple assessments, making it particularly sensitive to peaks in vascular tone rather than average resting state.
Inverse-normal transformation — converting raw values to a standardized normal distribution — is a statistical preprocessing step that satisfies GWAS model assumptions without changing the biological meaning of associations. Variants identified in this analysis affect the same underlying biological processes as those found in mean or baseline blood pressure studies.
The genetics behind diastolic blood pressure
Verma et al. (2024) identified 112 associated genes for maximum DBP in a large multi-ancestry meta-analysis. The top-ranked signals reveal a breadth of biological pathways:
FGF5 (rank 1 by gene prioritization) encodes fibroblast growth factor 5, the most replicated blood-pressure locus across global populations. FGF5 influences vascular smooth muscle tone through paracrine signaling loops and has been confirmed in European, East Asian, and South Asian cohorts across dozens of independent blood pressure studies. Its rank-1 position here confirms relevance across phenotype definitions.
BANK1 (rank 2) encodes B-cell scaffold protein with ankyrin repeats. BANK1 is primarily known as an immune signaling scaffold expressed in B lymphocytes that regulates B-cell receptor and toll-like receptor signaling. Its appearance in a blood pressure GWAS is a notable example of immune-vascular genetics: variants that subtly alter B-cell inflammatory signaling may shape the chronic vascular inflammation that drives arterial stiffness and elevated peak diastolic readings. BANK1 has also appeared in systemic lupus erythematosus GWAS datasets.
CCDC141 (rank 3) encodes coiled-coil domain-containing protein 141. CCDC141 has been associated with cardiac conduction intervals and developmental cardiovascular phenotypes. Its expression pattern in cardiac and vascular tissue makes it a plausible blood pressure candidate through effects on cardiac structural properties and output.
ANAPC4 (rank 4) encodes APC4, a core subunit of the Anaphase-Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase that controls cell cycle transitions. In vascular biology, cell cycle regulation governs smooth muscle cell proliferation and arterial wall thickening — contributors to arterial stiffness and elevated diastolic pressure.
TET2 (rank 5) encodes Ten-eleven translocation methylcytosine dioxygenase 2, an enzyme that converts 5-methylcytosine to 5-hydroxymethylcytosine — an early step in active DNA demethylation. TET2 is best known for clonal hematopoiesis of indeterminate potential (CHIP): somatic TET2 mutations in blood cells are the most common CHIP alteration and are strongly associated with cardiovascular disease risk and atherosclerosis. A germline blood pressure signal at the TET2 locus connects vascular epigenetic regulation to inherited diastolic BP — distinct from, but convergent with, the acquired CHIP biology.
Additional high-ranked genes include ZC3HC1 (nuclear interaction partner involved in cell cycle regulation; has appeared in coronary artery disease GWAS), WNT2B (a Wnt signaling ligand involved in vascular development), CHD6 (chromodomain helicase DNA-binding protein; transcriptional regulator), and SCN10A (voltage-gated sodium channel Nav1.8, with roles in cardiac conduction and adrenergic signaling).
Research snapshot: 112 genes identified for maximum diastolic BP by Verma et al. (2024). FGF5, BANK1, TET2, and ANAPC4 among the leading signals across vascular growth factor, immune, and epigenetic pathways. Research base: Robust.
What the research says
Verma et al. (2024), published in Science, conducted a large multi-ancestry GWAS across cardiometabolic traits. The maximum DBP phenotype captures genetic influences on peak vascular load — making it more sensitive than average-based phenotypes to variants that govern the upper boundary of arterial tone, including those acting through sympathetic activation and endothelial reactivity.
The 112-gene set is the broadest for any diastolic BP phenotype in this analysis series. This depth reflects both the statistical power of the study and the biological complexity of the maximum BP phenotype: peak readings are influenced by a wider array of cardiovascular regulatory systems than resting averages.
TET2's germline blood pressure signal is among the more biologically provocative findings. While CHIP-associated TET2 somatic mutations in blood cells raise cardiovascular risk through inflammatory mechanisms, the germline signal likely reflects TET2's role in regulating vascular smooth muscle gene expression programs through epigenetic mechanisms independent of CHIP.
How diastolic blood pressure affects you
Maximum diastolic BP captures the ceiling of arterial load. The FGF5 signal confirms a smooth muscle vascular growth-factor mechanism. BANK1's immune scaffold signal suggests that chronic B-cell vascular inflammatory tone may manifest as higher peak readings under physiological stress. TET2's epigenetic signal connects DNA methylation maintenance to vascular responsiveness.
TET2 and cardiovascular biology: Somatic TET2 mutations in blood cells are the most common form of clonal hematopoiesis and roughly double cardiovascular disease risk. The germline blood pressure signal at TET2 is a separate finding — but the convergence underscores TET2's central role across cardiovascular biology.
Working with your variant profile
Aerobic exercise, sodium restriction, and the DASH dietary pattern each reduce peak blood pressure readings as well as averages. For individuals whose results highlight FGF5 or BANK1 signals, the anti-inflammatory dimension of blood pressure management is particularly relevant. CCDC141 and cardiac development signals suggest monitoring cardiac structure as a complementary approach for those with additional cardiovascular risk factors.
Consult a licensed healthcare provider before making treatment decisions based on genetic results.
Related traits and genes
- Systolic blood pressure — FGF5, ZC3HC1, and many other genes shared
- Coronary artery disease — ZC3HC1, WNT2B, and BANK1 loci overlap with CAD datasets
- Systemic lupus erythematosus — BANK1 is a primary SLE susceptibility gene
- Clonal hematopoiesis (CHIP) — TET2 somatic mutations are the most common CHIP alteration
- Cardiac conduction — CCDC141 and SCN10A variants appear in QRS and arrhythmia datasets
Frequently asked questions
What does "maximum" mean in this blood pressure phenotype? It is the highest diastolic reading recorded across multiple measurement occasions. This captures peaks in arterial load rather than average resting state, making it more sensitive to genetic influences on vascular reactivity and sympathetic tone response.
What is inverse-normal transformation? A statistical preprocessing step that converts raw blood pressure values to a normal distribution to satisfy assumptions of linear GWAS models. The biological interpretation of associations is unchanged; only the scale of the raw data is transformed.
Why does BANK1 — an immune gene — appear in blood pressure genetics? BANK1 is a scaffolding protein in B-cell immune signaling. Variants that alter chronic B-cell inflammatory activity may shift the immune-inflammatory tone in arterial walls, contributing to endothelial activation and elevated peak diastolic readings. This immune-vascular axis is increasingly supported by GWAS findings across cardiovascular phenotypes.
What is TET2's role in blood pressure? TET2 is a DNA demethylation enzyme. In the context of blood pressure, germline TET2 variants likely affect vascular smooth muscle gene expression through epigenetic regulation. This is distinct from TET2's well-known role in clonal hematopoiesis, where somatic mutations in blood cells drive cardiovascular disease risk through inflammatory mechanisms.
Is FGF5 the same signal as in other diastolic BP studies? Yes. FGF5 is one of the most replicated blood pressure loci in human genetics. Its appearance as the top-ranked gene for maximum DBP confirms that FGF5's vascular smooth muscle growth-factor signaling is relevant across multiple blood pressure phenotype definitions.
What does the 112-gene count mean compared to other diastolic BP phenotypes? Maximum DBP has a richer genetic architecture because peak readings are influenced by more regulatory systems simultaneously — sympathetic activation, endothelial reactivity, cardiac output, and structural vascular properties all contribute. A broader gene count reflects this phenotypic complexity, not unusual individual genetic burden.
References:
- Verma A et al. (2024). PMID 39024449. Science.