Inherited disease and what genetic testing can uncover

Some diseases are inherited, carried from one generation to the next. This stems from the nature of genetics and how DNA is passed from parents to children.

When illness ‘runs in the family,’ it’s usually due to an underlying mutation in the genetic code. In some cases, a family history may be enough to justify an investigation by a medical professional. For many others, the arrival of symptoms is required to initiate supervised genetic testing. DNA testing helps the test-taker find out inherited diseases and helps them uncover any issues hidden in their DNA.

This is where at-home DNA kits can provide insight and spur proactivity about health and lifestyle. Testing for inherited diseases is easier than ever, but the results may not be as clear as you’d hoped. Understanding what a direct-to-consumer genetic test can reveal about your risk for disease is paramount for effective health choices.

The difference between a diagnosis and risk assessment

Genetic testing assesses your DNA and nothing else. The vast majority of diseases, like diabetes and cancer, aren’t specifically found in your genes. They’re diagnosed by tracking levels of proteins or other biomarkers like blood glucose or cell count.

However, mutations in DNA do directly cause some diseases. Most often, these illnesses are discovered early through postnatal testing or doctor-recommended investigations.

Inherited diseases with a single-gene origin

Mutations in the HTT gene cause Huntington’s Disease. It has a symptom onset around the ages of 30 to 50. A progressive, and eventually lethal, loss of brain cells characterizes the condition. It often begins with subtle changes in mood and mental abilities.

Cystic Fibrosis results from mutations in the CFTR gene. It is particularly prevalent among those with Northern European ancestry. The disease mainly affects the lungs but often involves other organs. It has a highly variable onset and symptoms.

Familial Hypercholesterolemia stems from mutations in the LDLR or ApoB genes. It is an inherited form of high cholesterol. The disease often doesn’t respond as well to lifestyle modifications, requiring medication. It is mostly symptomless until serious complications arise.

Carrier testing for familial disease

First of all, some diseases require a mutated copy of the gene from both parents to manifest. Having only a single copy is known as “carrier status.” This is the reason why some inherited illnesses seem to skip a generation. Cystic Fibrosis can be one such disease, with usually only mild or limited symptoms in carriers.

For new parents, or those considering children, an at-home DNA kit may be a useful first step in preparation. In the case of positive or inconclusive results, a more thorough screening should be pursued with a medical professional. This is almost always suggested, regardless if there is a family history of potentially inherited disease.

Complex or multi-gene disease

The vast majority of human diseases have no specific underlying cause. The concept of predictive medicine is to assess and reduce the risk of illness before it even appears. Until recently, science was primarily based on family history, lifestyle factors, and particular diagnostic tests.

At-home DNA kits usually provide insight on your risk of developing a particular ailment. Consequently, they do not return a binary yes-or-no answer. Along with a thorough family investigation, genetic testing can be a valuable asset in promoting healthy lifestyle choices.

However, given the lack of guidance from a genetic counselor or medical professional, it is vital to understand how these risk scores are generated.

Uncovering the root of disease with Genome-wide Association Studies

For diseases that aren’t explicitly connected with a mutation in a specific gene, recent technologies have allowed for extensive investigations of complex illness. The Human Genome Project was completed in 2003, a massive undertaking to sequence the entire human genome. For the first time, the genetic code of those with illnesses could be compared, en masse, to a standard ‘healthy’ genome.

The technique spawned the Genome-wide Association Study or GWAS. It’s an observational investigation, uncovering correlations between genetic mutations and expressed traits. For example, the DNA of those with glaucoma can be scanned for mutations that consistently deviate from a healthy, control genome. ‘Risk scores’ are assigned between mutations and the disease under investigation using sophisticated math and science.

Genetic Risk Scores for complex inherited disease

Most single mutations have no direct connections with a disease, nor do they significantly contribute to the risk of illness. However, combining dozens or even hundreds of these seemingly insignificant variants can result in a sizable risk score. This is certainly not a diagnosis or inevitability of disease, but it can guide healthy lifestyle choices.

For example, Glaucoma risk can be increased by hundreds of mutations in over ten different genes. Unfortunately, the vast majority of glaucoma cases do not include mutations in any of these genes. Other factors like diabetes, trauma, or infection are considered more reliable indicators of risk.

Cancer risk and at-home DNA kits

Another hot-button topic surrounding DNA test kits is to assess the risk of cancer development. Again, this is not a diagnosis or prognosis. It cannot replace or remove the need for screening or testing recommended for your age, lifestyle, or family history.

Most people have heard about the connection between the BRCA genes and a woman’s risk of breast cancer. While there are hundreds of known mutations in these two genes, only a hand-full have been connected to significantly increased risk of cancer. Further, only 5-10% of breast cancer cases involve mutations in the BRCA genes, making it an overall minimal influence on breast cancer risk.

Another commonly referenced gene is PTEN, often associated with prostate cancer and an overall predisposition to cancer risk. Over 70 mutations in the gene can cause Cowden Syndrome, an inherited illness that causes growths that may eventually develop into cancerous tumors.

Screening inherited disease at home

Finally, at-home DNA kits are not meant to be diagnostic. This is reflected in the results you may receive after completing the test. In most cases, shocking or surprising outcomes are rare; many genetic diseases are found in childhood or early adulthood.

Genetic testing excels at defining your genetic risk of more complex disease. It’s an ideal first step in being proactive about your health.

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