How do Hundreds of Your Genetic Variants Impact Your Heart Health?

Niha Zubair, Arivale Clinical Research Scientist, PhD
Niha Zubair
Arivale Clinical Research Scientist, PhD

Research shows that your heart health can be influenced by hundreds, maybe even thousands, of individual genetic variants. And as research on the human genome advances, it’s likely that scientists will discover even more.

We all have many genetic variants with potential positive or negative effects on our heart health, but individually, each of these variants only has a minor impact. However, when taken together, the impacts of these variants add up, and each person’s potential predisposition can vary greatly.

Because Arivale analyzes your whole genome sequence, it’s possible for us to do just this—gauge potential predisposition by looking at hundreds of your genetic variants.

This month, Arivale is unveiling new lipid polygenic profiles, calculating your potential predisposition for high LDL cholesterol, low HDL cholesterol, and high triglycerides—all of which impact your overall heart health.

On your dashboard, Arivale already provides more in-depth reporting on your lipid profile than you might get from your healthcare provider. Synthesizing data on markers like LDL particle number, LDL small particle number, Oxidized LDL, and Triglyceride HDL ratio allows our clinical team and health coaches to gain a nuanced, complex view of your heart health—which wouldn’t be possible by simply looking at total cholesterol. The new polygenic profiles will enrich this view even more.

Before we dive into the science behind the lipid polygenic profiles, let’s explore blood lipids and why measuring them can provide insights into your heart health today, and more importantly, as you age.

What’s in a blood lipid?

Cholesterol is something we often hear about in a negative context—a number your doctor may want you to decrease, a percentage on a nutrition label. But in reality, our bodies’ relationship to cholesterol is much more complex.

A wax-like substance, cholesterol is found in many foods (namely, animal products like eggs yolks, dairy, and meat) and is also produced by our bodies. Despite the mostly negative reputation, it’s important to understand cholesterol itself isn’t bad. We actually need it to perform many biological functions, such as converting sun exposure on our skin to Vitamin D. However, like all things, too much cholesterol (especially LDL) can increase your risk for heart disease.


LDL is commonly labeled as the “bad” cholesterol, and it carries cholesterol to all parts of the body. Some LDL is necessary; however, too much LDL can cause a buildup of cholesterol in the artery walls (otherwise known as atherosclerosis), which can lead to coronary artery disease. Saturated fats such as those found in cheese, full-fat dairy, meat, coconut and palm oils can increase LDL.


HDL is commonly labeled as the “good” cholesterol. It removes cholesterol from the bloodstream and artery walls. In other words, it essentially cleans up after LDL. An elevated level of HDL can protect against heart disease, while a low level puts us at risk. Aerobic exercise can increase HDL, while trans fats, such as hydrogenated oils commonly found in processed foods, can decrease it.


The cholesterol that circulates in your blood is packaged with a type of fat called triglycerides. They are the most common type of fat found in our blood and serve as a source of energy. We can obtain triglycerides from food, and our bodies also produce it. If you consume more calories than you need, they get stored as triglycerides. Elevated triglycerides in the blood are associated with atherosclerosis and subsequently heart disease. Refined carbohydrates and alcohol increase triglycerides.

To optimize heart health,  we’d like to keep LDL and triglyceride levels low and HDL levels high. In the past, the American Heart Association’s treatment guidelines directed healthcare providers to focus on treating their patients’ cholesterol to target levels. However, current prevention guidelines recommend an approach that goes beyond cholesterol levels alone and considers overall risk assessment (age, family history, smoking, high blood pressure, lifestyle, etc.).

Blood lipids, meet your genetics.

LDL, HDL, and triglycerides are influenced by hundreds, maybe thousands, of common genetic variants, as well as your diet and lifestyle. Scientists at Arivale utilized published scientific research and your Whole Genome Sequencing data to create a personalized polygenic profile for each of these lipid traits.

We’ve talked about the details of polygenic profiles in a previous blog post, but, briefly, a polygenic profile is the sum of the effects of all the common genetic variants implicated for a quantitative trait (e.g. LDL cholesterol) that are observed within you.

The advantage of a polygenic profile is that it gives you more insight into your potential genetic predisposition for a trait than any single common genetic variant.

The three lipid polygenic profiles are based on data from a Genome Wide Association Study (GWAS) conducted by the Global Lipids Genetics Consortium. They did a meta-analysis of 60 studies totaling up to 188K people and tested over 2.4 million common genetic variants for association with LDL, HDL, and triglycerides separately. Arivale scientists selected a subset of non-redundant genetic variants for each profile based on their statistical significance in the GWAS. Roughly 800 genetic variants across your whole genome are included in each of these polygenic profiles!

Genes are not your destiny.

A high LDL polygenic profile doesn’t necessarily mean you have a high LDL level. Similarly, a low HDL polygenic profile doesn’t necessarily mean you have a low HDL level. These profiles only tell you about your potential genetic predisposition, not what is actually happening in your body. For that, Arivale looks at your HDL, LDL, and triglycerides as well as many other lipid biomarkers mentioned above.

Lastly, it’s important to remember your lifestyle has a strong impact on your heart health. While genetics provide context, diet and exercise are often the change-makers and you have control over this piece. But you certainly don’t have to go it alone. At Arivale, our coaches will recommend a custom action plan designed to empower you to reach your optimal lipid levels.

Please visit your dashboard to see your unique lipid polygenic profiles and also how you compare to the other Arivale Pioneers.  An Arivale Coach will discuss these new insights with you on your next coaching call. Please let us know how we can make this information more actionable and useful for you!


Global Lipids Genetics Consortium. Discovery and refinement of loci associated with lipid levels. Nature genetics. 2013 Nov 1;45(11):1274-83.