Penetrance and Expressivity Impact Genetic Reporting
You’re looking at your medical or recreational genetic report and it says: “you are tall and handsome,” or: “pretty and petite,” and maybe you’re not! You get the point, sometimes genetic reports have predictions that do not seem accurate. And, then on a more serious note, your report may scare the daylights out of you by pointing out that you are at risk of some deadly disease. How can you, or should you, trust this company’s report if it is not even nailing down the less important predictions? Read on, and you will better understand why it is so important for your health.
One part of this answer has to do with genetic penetrance, which is the percentage of people with a genetic variant that have a particular disease or trait. Our genetics can be very complicated, with each person having a different set of millions of genetic variants that interact with each other in ways we do not yet fully understand. Sometimes if you have a dangerous variant, it’s impact may be eliminated by other genetic variants, or by reducing your environmental exposure.
The severity of symptoms associated with a variant is called expressivity. For those with a variant, symptoms can range from severe, moderate, or might not even be noticeable. This is called variable expressivity.
Food selection is clearly an environmental exposure that can be controlled, and works with genetic variants to affect both penetrance and expressivity, which is the focus of Food Genes and Me.
Let’s take a look at some notable examples. Neurofibromatosis is a disease that causes reddish-brown spots on the eyes, benign skin tumors, and several other conditions. There are variants that are in 100% of affected people - this is called complete penetrance, where all individuals get the disease. When variants have high penetrance, they are generally called mutations. The number and severity of symptoms can vary among people and is called the expressivity of the variant.
BRCA1 is a gene that is commonly tested for variants that might cause breast and ovarian cancers. Patients with these inherited variants might go as far as to have a mastectomy or ovariectomy to reduce their risk of disease. However, one BRCA1 study shows that only 48 of one hundred people will get one of these cancers by age 80. Thus, the penetrance is 48% by age 80. Other studies vary, but have similar variable penetrance.
My relative had a report that pointed out a variant for Lynch syndrome, which produces many cancerous polyps in the large intestine. But, he was 93 and doing well! He had routine colonoscopies, but only occasionally had a few polyps removed over many visits – not what his report suggested. This is where science gets grayish. By the criteria used in most studies, this would not be considered cancer. Nevertheless, the fact that he had vastly reduced numbers of polyps for someone with this variant is an example of reduced expressivity.
The millions of variants that each of us possess do really matter, after taking into account penetrance and expressivity. However, we are just in our infancy understanding penetrance and expressivity, which can show up as seemingly inaccurate statements in genetic reports.
Moving on to diet, let’s talk lactose intolerance, where dairy foods containing lactose can induce abdominal pain, bloating and other symptoms. The different human populations tend to have different levels of penetration and expressivity of variants that cause lactose intolerance. This is why 92% of Chinese and 75% of African Americans adults, while only 10% of Northern Europeans, have lactose intolerance. This is one example of why we need personalized diets!
Today, common practice is to define the percentage of people with a particular variant. If you are at moderate or high risk you should consult a Genetic Counselor or Dietician and set up a screening schedule. This type of preventative strategy may be the best approach to reduce the burden of disease in the near future.
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