What does a higher cardiovascular disease risk result mean?

A higher result means that the combination of genetic variants in your ExomeDNA data, across loci associated with cholesterol absorption, vascular remodeling, and cardiac signaling, has been statistically linked with elevated cardiovascular disease likelihood in large population studies. It does not mean you will develop heart disease — it describes a polygenic tendency observed at the population level, which lifestyle and clinical management can substantially modify.

Which genes are most important for cardiovascular disease risk in my result?

Two genes carry the most direct mechanistic evidence for this trait in the authorized gene set. ABCG8 governs how efficiently dietary cholesterol is absorbed through the intestinal wall. ADAMTS7 is a metalloprotease in arterial tissue whose activity promotes the matrix remodeling that underlies plaque development; it is one of the most replicated cardiovascular GWAS loci identified to date.

Can I reduce my cardiovascular disease risk even with a higher genetic score?

Yes. Aerobic exercise, a Mediterranean or DASH dietary pattern, smoking cessation, blood pressure management, and lipid control each carry large independent effect sizes on cardiovascular outcomes. Research consistently shows that people with elevated polygenic risk who adopt multiple healthy behaviors can reduce their absolute risk substantially.

How does the ABCG8 gene affect cholesterol and heart health?

ABCG8 encodes half of a sterol transporter that pumps cholesterol and plant sterols out of intestinal cells and liver hepatocytes. Variants that reduce transporter activity allow more cholesterol absorption, raising LDL and accelerating the plaque-building process in arterial walls.

What is ADAMTS7 and why does it matter for heart disease?

ADAMTS7 is a metalloprotease that breaks down structural proteins in the arterial wall. Elevated ADAMTS7 activity degrades the extracellular matrix, creating conditions favorable for atherosclerotic plaque formation and arterial stiffening. The chromosomal region containing ADAMTS7 is one of the most consistently replicated loci in cardiovascular GWAS research.

How does the ADH1B gene connect to cardiovascular risk?

ADH1B encodes the primary enzyme responsible for breaking down ethanol into acetaldehyde. Variants that produce faster metabolism tend to reduce voluntary alcohol consumption, which reduces long-term cardiovascular harm from heavy drinking. Because sustained heavy alcohol use raises blood pressure and contributes to cardiomyopathy, ADH1B variants offer indirect but meaningful information about one channel of cardiovascular risk.

Cardiovascular Disease Risk and Your Genetics

Name: Cardiovascular Disease Risk Genetics
Creator: Scott Peeples
Published: 2026-05-29

Written by Scott Peeples, BS Biomedical Sciences · ExomeDNA Founder Reviewed by ExomeDNA Editorial Process Last reviewed: 2026-05-29

This page contains general information only. For personal health decisions, consult a qualified clinician.

What is cardiovascular disease risk?

Cardiovascular disease (CVD) is a broad category encompassing coronary artery disease, heart failure, stroke, and peripheral arterial disease — and it remains the leading cause of death globally, accounting for roughly 17.9 million deaths each year. Risk is shaped by a combination of lifestyle factors (diet, activity, smoking) and a substantial inherited component that influences how the body manages cholesterol, arterial integrity, and cardiac signaling. Below: an evidence-based look at the genes, mechanisms, and modifiable factors relevant to your ExomeDNA cardiovascular disease risk result.

The genetics behind cardiovascular disease risk

Cardiovascular disease is among the most-studied complex traits in human genetics, with thousands of genome-wide association study (GWAS) loci catalogued to date. Two principal biological pathways emerge from the genes authorized for this trait.

Cholesterol and sterol handling — ABCG8

ABCG8 encodes a sterol transporter that pairs with ABCG5 to shuttle cholesterol and plant sterols out of intestinal cells back into the gut lumen and out of liver hepatocytes into bile. This transporter sits at a critical control point: how efficiently dietary cholesterol is absorbed before it can enter circulation. Variants in ABCG8 that reduce transporter activity allow more cholesterol to cross the intestinal wall, raising LDL, accelerating atherosclerosis, and increasing cardiovascular risk. The same gene is associated with gallstone susceptibility — a reminder that cholesterol metabolism has system-wide consequences, not only cardiac ones.

Extracellular matrix remodeling and plaque formation — ADAMTS7

ADAMTS7 is a metalloprotease expressed in vascular smooth muscle cells and macrophages. Its primary substrates in the arterial wall include versican and COMP — large extracellular matrix proteins that help maintain vessel structure. When ADAMTS7 activity is elevated, it degrades the matrix scaffolding that normally restrains smooth muscle cell migration and inflammatory infiltration. The result is accelerated plaque development and a less stable arterial architecture. The ADAMTS7 locus at chromosome 15q25 is one of the most consistently replicated findings in cardiovascular GWAS research, having appeared in numerous independent large-scale studies across diverse populations.

Alcohol metabolism — ADH1B

ADH1B encodes alcohol dehydrogenase 1B, the enzyme primarily responsible for converting ethanol to acetaldehyde. Variants in ADH1B alter how rapidly this conversion occurs. Fast-metabolizer variants tend to produce acetaldehyde quickly, generating flushing and discomfort that reduces voluntary alcohol intake — and with it, the long-term cardiovascular damage associated with heavy drinking. Slow-metabolizer variants show the opposite pattern. Because heavy alcohol consumption is itself a significant cardiovascular risk factor — raising blood pressure, promoting cardiomyopathy, and disrupting cardiac rhythm — ADH1B genetics provide an indirect but meaningful window into alcohol-related cardiovascular risk.

Cardiac signaling — ADCY9 and ADK

ADCY9 (adenylyl cyclase 9) produces cyclic AMP in response to G-protein-coupled receptor stimulation, including beta-adrenergic signaling that governs heart rate and vascular tone. ADK (adenosine kinase) regulates the concentration of free adenosine in cardiac tissue; adenosine is cardioprotective, reducing ischemic injury during periods of reduced blood flow. Variants in these genes affect the sensitivity and resilience of cardiac signaling networks.

Membrane transport context — ABCC10, ABCF3, AAGAB, ADCY9

ABCC10 and ABCF3 are members of the ATP-binding cassette transporter family with roles in lipid metabolism and membrane transport. AAGAB participates in clathrin-coated vesicle trafficking, a process relevant to receptor recycling in endothelial and smooth muscle cells. While these genes contribute smaller individual effect sizes, they illustrate the polygenic architecture of CVD — risk is distributed across many variants, each adding a modest increment.

What the research says

Research base: Robust.

Cardiovascular disease genetics is among the best-characterized areas of complex trait genomics. Large-scale GWAS studies have identified thousands of associated loci, and polygenic risk scores for CVD now have sufficient power to stratify meaningful risk differences across populations.

ADAMTS7 is one of the most replicated CAD/CVD GWAS loci. The chromosome 15q25 region containing ADAMTS7 has appeared in multiple independent large-scale studies, supporting a causal role for matrix remodeling in atherosclerotic plaque development.¹

Research published in 2019 demonstrated that integrating polygenic functional enrichment substantially improves the statistical power of GWAS to detect risk loci for complex traits including cardiovascular disease — meaning that the genetic architecture of CVD extends far beyond the top-ranked individual variants, with many smaller-effect loci contributing meaningfully to overall risk.²

Work examining non-additive genetic associations published in 2021 found that gene-gene interaction effects contribute to the architecture of age-related complex diseases including cardiovascular conditions, suggesting that the inherited component of CVD is more nuanced than simple additive risk accumulation across loci.³

Aerobic exercise reduces major cardiovascular events by approximately 35% in meta-analyses of randomized controlled trials — one of the largest effect sizes observed for any lifestyle modifier of CVD risk, reinforcing that genetic predisposition is not destiny.

The convergence of genetic evidence, epidemiological data, and clinical trial results supports a model in which CVD risk is meaningfully heritable but substantially modifiable. Polygenic risk combined with traditional risk factors (blood pressure, lipids, smoking, activity) provides the most complete picture available.

References

Kichaev G et al. 2019. Leveraging Polygenic Functional Enrichment to Improve GWAS Power. PMID: 30595370.
Guindo-Martínez M et al. 2021. The impact of non-additive genetic associations on age-related complex diseases. PMID: 33893285.
Guo Y et al. 2023. Genome-Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Disease. PMID: 37947095.

Data sources: GWAS Catalog, Open Targets Platform, ClinVar, ClinGen (accessed 2026-05-29).

How cardiovascular disease risk affects you

A higher polygenic risk result for cardiovascular disease reflects a combination of inherited variants — across pathways including cholesterol absorption (ABCG8), arterial wall integrity (ADAMTS7), cardiac signaling (ADCY9, ADK), and alcohol metabolism (ADH1B) — that in aggregate have been associated with elevated CVD likelihood in large population studies.

It is important to hold this result in context. Polygenic risk scores describe statistical tendencies observed across populations. Many people with elevated genetic risk never develop significant cardiovascular disease, while many people with lower genetic risk do — because lifestyle, environment, and clinical management account for a large share of actual outcomes. The genetic result is one input into a broader picture, not a forecast.

For those experiencing elevated cardiovascular genetic risk scores, the most useful response is not alarm but attention: treating the result as a signal to engage meaningfully with the modifiable factors that have the strongest evidence base. Blood pressure control, lipid management, physical activity, and smoking status each carry larger individual effect sizes on cardiovascular outcomes than most single genetic variants. The genetic result adds context about which biological pathways may warrant closer monitoring.

CVD risk is also cumulative and time-sensitive. The earlier lifestyle modifications are adopted, the greater the benefit — atherosclerosis is a process that develops over decades, and earlier intervention in the cholesterol and vascular remodeling pathways (directly implicated by ABCG8 and ADAMTS7) has disproportionate impact on long-term outcomes.

Working with your cardiovascular disease risk result

The following evidence-backed modifiers are relevant to the genetic pathways implicated in this result.

Adopt a Mediterranean or DASH dietary pattern. Both eating patterns consistently reduce LDL cholesterol, blood pressure, and incident cardiovascular events in randomized trials. Reducing saturated fat intake directly addresses the ABCG8 cholesterol absorption pathway by reducing the cholesterol load presented to the intestinal transporter — a particularly relevant modifier for those with absorption-increasing variants.
Accumulate 150 or more minutes of moderate aerobic activity per week. This threshold, supported by multiple large meta-analyses, corresponds to approximately a 35% reduction in major cardiovascular events. Aerobic exercise reduces blood pressure, improves lipid profiles, promotes vascular elasticity, and reduces systemic inflammation — addressing the matrix remodeling and arterial stiffness mechanisms implicated by ADAMTS7.
Eliminate or substantially reduce tobacco use. Smoking is the single most impactful modifiable cardiovascular risk factor, responsible for a disproportionate share of attributable CVD events globally. For people experiencing elevated genetic risk across multiple pathways, compounding that risk with tobacco exposure significantly accelerates plaque development and endothelial injury.
Monitor and manage blood pressure proactively. Hypertension is the leading attributable risk factor for cardiovascular mortality worldwide. For those with genetic variants that affect vascular smooth muscle behavior and cardiac signaling (ADAMTS7, ADCY9), maintaining blood pressure in the normal range is especially load-bearing. Home monitoring and regular clinical checks provide early detection of developing hypertension before cumulative arterial damage occurs.
Moderate or eliminate alcohol consumption, particularly heavy episodic drinking. ADH1B variants affect how alcohol is metabolized — but regardless of genotype, heavy alcohol use significantly raises blood pressure, promotes cardiac arrhythmia, and contributes to cardiomyopathy over time. The ADH1B genetics provide context for how alcohol is processed, but the evidence for harm reduction at elevated consumption levels is genotype-independent.
Engage with lipid management in partnership with a clinician. ABCG8 variants that increase cholesterol absorption may translate to persistently elevated LDL even with dietary optimization. Statin therapy and other lipid-lowering interventions are among the most evidence-dense interventions in cardiovascular medicine. A clinician can assess whether pharmacological lipid management is appropriate in the context of your full cardiovascular risk profile.

The genetic architecture of cardiovascular disease overlaps with several related traits assessed by ExomeDNA, including LDL cholesterol levels, HDL cholesterol levels, blood pressure, and body mass index. Variants in ABCG8 are also associated with gallstone risk — a direct consequence of the same sterol transport function that influences cardiovascular cholesterol handling.

ADAMTS7 variants overlap with coronary artery disease and arterial stiffness phenotypes. ADH1B variants are shared with alcohol metabolism and alcohol use traits. ADCY9 contributes to heart rate regulation phenotypes. Reviewing related traits provides a more complete picture of your inherited cardiovascular profile than any single result in isolation.

Frequently asked questions

See below for expanded answers.

ExomeDNA genetic results are for wellness and educational purposes only. Consult a clinician for personalized health guidance.

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