a gene-ius report
Our report is easy to understand, but it's scientifically sound and action-oriented. It's divided into five parts: carrier status of rare diseases, risk of common diseases, drug response (pharmacogenetics), ancestry, and traits and wellness. The best feature is the personalized recommendations we include for each health finding to help you prevent diseases and maintain a healthy lifestyle.
We know genetics can be complicated, so our report is detailed (about 50 pages) but clear and straightforward. If you have any questions, don't worry! You'll get Nuclein Health 101: Understanding Your Results, a guide explaining genetics basics, diseases, references, and more. This guide is designed to help you fully understand your test results and what they mean to you.
Want to know more about what's in the report? Keep reading, or take a look at a demo report.
carrier status of rare diseases
Rare diseases, also known as monogenic diseases, are caused by changes in a single gene. They're often called Mendelian, named after the patterns of inheritance discovered by Gregor Mendel: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and Y-linked.
There are about 8,000 known rare diseases. A disease is considered rare if it affects fewer than 1 in 2,000 people. However, globally, as many as 1 in 10 or 1 in 15 people might have a rare disease. Many of these conditions are recessive, meaning most of us carry at least one rare disease gene without knowing it.
Being a carrier means you have one copy of a gene variant linked to a disease. If the disease is autosomal recessive, you won’t usually get sick, but you could pass the variant to your children. If it’s autosomal dominant, having just one copy of the variant can cause illness.
Carrier screening tests identify if you’re a carrier of a gene variant that could lead to a rare disease in your children. This information is crucial for family planning, offering options like preimplantation genetic testing.
Autosomal Dominant Monogenic Diseases: These diseases occur when an individual inherits one copy of a mutated gene, making them a heterozygote. This mutated gene is known as a disease-causing (pathogenic) heterozygous variant. Having just one of these variants is sufficient to cause the disease, regardless of the presence of the other “healthy” copy. The pathogenic variant can be inherited from a parent affected by the disease or arise spontaneously during embryonic development, known as a de novo variant.
Examples: Brugada syndrome, Cardiomyopathies, Familial Hypercholesterolemia, Li-Fraumeni syndrome, Hereditary breast/ovarian cancer, Marfan Syndrome, Neurofibromatosis Type 1, Polycystic kidney disease (PKD), Retinitis Pigmentosa, Osteogenesis Imperfecta, and many more.
Autosomal Recessive Monogenic Diseases: In these cases, an individual inherits two copies of a mutated gene, making them a homozygote for the disease-causing (pathogenic) variant. In some instances, the disease can also develop when an individual inherits two different pathogenic heterozygous variants in the same gene, one from each parent, creating a compound heterozygote. Individuals with a heterozygous pathogenic variant for a recessive disease, known as carriers, typically don’t show symptoms of the disease.
Examples: Gaucher Disease, Wilson Disease, Cystic Fibrosis, Familial Mediterranean Fever, Tay-Sachs Disease and many more.
Monogenic Diseases on the X and Y Chromosomes: These diseases have distinct inheritance patterns due to the difference in chromosome complement between males and females.
X-Linked Recessive Diseases: Women (XX) with an X-linked recessive disease inherit one mutated copy from the affected father and the second mutated copy from the mother, who may often only be a carrier (heterozygote) or may also be affected (homozygote), although less often. Men (XY) with an X-linked recessive disease inherit a single copy of the X chromosome from their mothers, which means they will always inherit the pathogenic variant from their mothers. Because they don’t have a second healthy copy to counteract the effect, they are more likely to be affected by X-linked recessive diseases.
Examples: Haemophilia, Duchenne Muscular dystrophy, Becker Muscular Dystrophy and so on.
X-Linked Dominant Diseases: Not many diseases follow this pattern. Women with an X-linked dominant disease can inherit the pathogenic variant from the affected mother or father, while men always inherit it from the affected mother. The variant always leads to the onset of the disease.
Examples: Alport syndrome, Rett syndrome, X-linked Hypophosphatemia and so on.
Y-Linked Diseases: These are even less common and only affect men because they have a Y chromosome. Y-linked monogenic diseases are always passed down from fathers to sons, and the pathogenic variants always lead to disease onset.
Examples: Nonobstructive Spermatogenic Failure, Retinitis Pigmentosa linked to the RPY gene, and more.
risk of common diseases
Common diseases don't have a single genetic cause. They result from the combination of many genetic variants. These variants alone are not impactful, but together, they significantly increase disease risk. We call these "polygenic" or "complex" diseases. They're influenced by both genetics and environmental factors. Understanding these factors is key to developing prevention strategies.
In the past, linking genetic variants to common diseases was very difficult. Now, thanks to advanced genomic technologies and data analysis, we have genome-wide association studies (GWAS). GWAS help identify many genetic variants that, collectively, increase disease risk. This enables the calculation of an individual’s Polygenic Risk Score (PRS).
The calculation of PRS involves examining hundreds of thousands of genetic variants. Each of these slightly increases or decreases your risk for specific diseases. By adding up their combined effects, we scientists can estimate your overall genetic risk for a particular common disease.
Disease risk stratification is like sorting. Based on your PRS, you can be categorized into different risk levels for certain diseases – low, moderate, or high risk. This doesn’t mean you will definitely develop the disease if you have a high risk, but it indicates that your genetic makeup might make you more susceptible compared to others.
A high PRS means that you have a greater risk of getting a disease compared to most other people. For instance, if your PRS for a specific disease is in the 95th percentile, it means your score is higher than 95% of the scores in the population. This would classify you into a high-risk group.
The idea behind risk stratification is to figure out who is more likely to get a particular disease. This way, we can personalize how we approach their healthcare. People at a higher risk can benefit from early interventions, preventive actions, and treatments. Plus, when individuals know they have a higher risk, they’re often more motivated to make lifestyle changes and seek preventive care.
Examples:
- Coronary Heart Disease (CHD): If someone is at a high risk of CHD, they might be advised to take preventive medications, make lifestyle changes like regular exercise, a healthy diet, and quitting smoking, and maintain healthy body weight and cholesterol levels. These changes can prevent the need for surgeries like carotid endarterectomy, coronary artery bypass, and costly treatments.
- Type 2 Diabetes: For those at high risk of type 2 diabetes, advice could include maintaining a healthy weight, balanced eating, regular physical activity, and regular blood sugar monitoring.
- Prostate Cancer: High-risk individuals might be advised to have regular prostate exams, screenings, and monitor tumor marker levels while adopting a healthy lifestyle.
- Alzheimer’s Disease: Those at high risk of Alzheimer’s may be encouraged to engage in brain-boosting activities like regular exercise, a healthy diet, and mental challenges like puzzles, learning a new language, or playing an instrument.
In essence, risk stratification helps tailor healthcare advice to individuals, promoting early action and healthier lifestyles to reduce the chances of developing these diseases.
To calculate your Polygenic Risk Score (PRS) we use a statistical method called imputation and estimate the genotype of variants not analyzed with our test, by
leveraging patterns of genetic variation in a reference population, as determined with Genome-Wide Association Studies (GWAS). This allows us to expand the
number of analyzed variants from ~750,000 to ~13 million, providing a wider and more accurate assessment of your potential risk of common diseases.
Imputation in genetics is a key statistical technique for predicting unknown (untested) genetic data. This method is essential when DNA tests, like the GenoScope, don’t analyze every genetic variant. GenoScope tests about 700,000 variants, but what about the untested ones?
Here’s where imputation comes in, using reference panels – databases of genetic sequences – to infer missing data in your genome. It’s like solving a jigsaw puzzle by referring to similar completed ones. This analogy explains how imputation fills the gaps, particularly with Single Nucleotide Polymorphisms (SNPs), the most common genetic variants
This technique boosts the accuracy of Polygenic Risk Scores (PRS), which sum up the effects of hundreds of thousands of SNPs to predict disease risks. Without imputation, PRS might miss key SNPs, leading to incomplete or less accurate results. This is crucial for understanding complex diseases like heart disease, diabetes, or certain cancers, where numerous genetic factors are involved. Imputation, by predicting missing SNPs, offers a more comprehensive view of an individual’s genetic risk, aiding in personalized healthcare and potentially better health outcomes.
drug response (pharmacogenetics)
Doctors often choose a medication from a group of drugs and prescribe a standard dose based on your age, weight, and gender. But here's the catch: different people react differently to the same drug! Pharmacogenetics is the study of how your genes affect your response to drugs. By looking at your genetic makeup and how it influences drug metabolism, pharmacogenetic testing can help doctors give you the right treatment. This means you can get better results from your medication, while decreasing the risks of side effects.
- Better Effectiveness: It helps find the right drug and dose for you based on your genes, making treatment more effective.
- Better Safety: It reduces the risk of side effects by identifying if you’re more likely to have them, making treatment safer.
- Improved Health: Customized and tailored treatment plans can lead to better results and improved overall health.
- Cost Savings: By avoiding treatments that won’t work, it saves you money on ineffective options.
Everyone!
Blood-Thinning Drugs:Â Some variants affect how these drugs work, impacting effectiveness and raising the risk of side effects, like stent blockage.
Mental Health Drugs: Some variants make people more prone to side effects from mental health drugs, such as antipsychotics or antidepressants.
Cancer Treatment Drugs: Some variants influence how chemotherapy drugs are processed, affecting how well they work and increasing side effects.
Asthma Drugs: Some variants alter how asthma drugs are metabolized, which might affect their effectiveness and raise the risk of side effects.
HIV Drugs: Some variants can make individuals more susceptible to side effects from specific HIV medications, like protease inhibitors.
…and many more examples where pharmacogenetics can make a big difference in the effectiveness and safety of medications for different people.
ancestry
Where in the earth are you from? Knowing your ancestry can be a fun way to learn more about yourself. It can help you imagine how your ancestors may have lived and how they migrated and evolved, focusing on specific regions and populations.
Another interesting aspect of ancestry testing is the detection of traces of Neanderthal DNA in modern humans. Early humans interbred with Neanderthals, and as a result, people today have Neanderthal DNA in their genomes!
wellness & traits
What makes you stand out from the crowd? We delve into the quirks that make you... well, you! Learn more about the physical and behavioral aspects that make you unique.
Curious to know if you're a natural redhead or a brunette at heart? Our test might reveal your potential for specific athletic abilities, like endurance or power. Wondering why you're tall or short? We've got answers for that too!
But our test isn't just about appearances. Dive deeper into your behavioral traits and preferences. We can shed light on your likely sleep patterns and much more.
And don't forget about life's earthly pleasures – our test uncovers your preference or sensitivity to various tastes and flavors. Are you a fan of sweet treats, or do savory snacks hit the spot? Maybe you can't live without caffeine? Let's find out together!