Risk Assessment

What you will learn:

  • Define genetic risk
  • Recall how to calculate genetic risk
  • Discuss residual risk

Genetic risk: Determining the likelihood of a condition or disease

When risk is described, it's explained with words such as chance or likelihood.

"Risk" is the chance that a something will happen. When there is a chance for something to happen, there is also a chance that it won't happen. If those chances are the same, people may say the chances are "50-50."

There are multiple kinds of risks that will be discussed in Mayo Clinic GeneGuide™:

  • Population risk is the predicted chance that you carry a variant based on your race or ethnic background. For example, the population risk of people with a non-Hispanic white background and no family history of cystic fibrosis is 1 in 25 for carrying a variant in the CFTR gene.
  • Residual risk is the chance that you still have a variant even AFTER you have normal genetic test results, based on the test not picking up all possible variants. In non-Hispanic white people with normal Mayo Clinic GeneGuide™ carrier testing for cystic fibrosis and no family history, the residual risk of still carrying a CFTR gene variant is 1 in 200.
  • Some of your Mayo Clinic GeneGuide™ results may indicate that you have an increased risk of developing a condition due to having a gene variant or nongenetic lifestyle factors. How big that actual risk is depends on what variant you have and your nongenetic factors.

Genetic risk is a calculation used to determine the likelihood or chance a person will develop a genetic condition or be a carrier for a genetic disease. Genetic risk uses all available information, such as your population risk, and then further refines your risk based on your family, medical and pregnancy history, and your results from any relevant tests.

Associations versus risk factors

Conditions are said to be "associated" if they occur together more often than chance would predict. Associations between two conditions occur in the same person, but they may or may not cause each other.

  • People with asthma often have hay fever. Asthma does not cause hay fever, and hay fever does not cause asthma. They may have a common causative environmental factor. Asthma and hay fever are associated with each other.
  • Childhood is associated with getting measles, but being young does not cause measles. Older people are less likely to get measles because they either had measles already or were vaccinated already.
  • Some genetic variants are found more often in people with asthma than in people without asthma. These variants are "associated" with asthma. However, the actual variants may or may not be the direct cause of the asthma but may be just nearby a gene variant that causes asthma.

Calculating genetic risk

Genetic risk can be calculated with or without your having had any genetic testing. The more information available about you, the more accurate your genetic risk calculation will be.

Here's an example of the genetic risk to be a carrier of the autosomal recessive condition cystic fibrosis (CF).

Calculating genetic risk

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Scenario 1: No history of or testing for CF

A healthy non-Hispanic white female, Mary, has a 4 percent (1 in 25) chance to be a carrier of a variant in the cystic fibrosis gene (CFTR).

  • That means there is a 96 percent (24 in 25) chance for Mary to not carry a CFTR gene variant.
  • These risks are based on known population risks.

Scenario 2: Family history important

  • Mary has a first cousin, Joe, who has cystic fibrosis.
  • Based on this family history information, Mary's calculated risk to be a carrier is 25 percent (1 in 4). See calculation example.
  • This means there is a 75 percent (3 in 4) chance that Mary is not a carrier.
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Here is how the risk was calculated in scenario 2 based on family history:

  • Mary's aunt (Joe's mom) must be a carrier to have had an affected child.
  • Therefore, Mary's Dad's chance to carry the variant is 1 in 2 and, if he is a carrier, he would have a 1 in 2 chance to pass the variant down to Mary.
  • Multiply 1/2 x 1/2, and the result is 1/4 (1 in 4) or 25 percent, which is Mary's chance to be a cystic fibrosis carrier, if she has a cousin with cystic fibrosis.

Calculating genetic risk

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Scenario 3: Family history positive for CF plus carrier screening negative for CF

  • Mary had cystic fibrosis carrier screening and the results were negative (no CFTR variant found). The Mayo Clinic GeneGuide™ carrier screening for cystic fibrosis finds 90 out of 100 people who are carriers.
  • The chance of Mary being a carrier is now reduced to approximately 3 percent (1 in 40) because after carrier screening a 1 in 10 chance remains that there is a CFTR variant that we cannot detect. Therefore, 1/4 x 1/10 = 1/40.

Calculating genetic risk

  • The chance is greater than 97 percent (39 in 40) that Mary is not a carrier.

There are still further ways to refine Mary's risk of being a carrier. This all depends on how much information Mary is able to obtain about her first cousin Joe and his condition.

Residual risk: It is never zero

Residual risk is the percent chance of still carrying a variant after genetic testing is negative.

  • In many cases, genetic testing is not absolute (that is, it's not 100 percent sensitive).
  • Therefore, even if your genetic testing is negative, there remains a residual chance of carrying a variant.
  • In the above example, even though Mary's cystic fibrosis carrier testing is negative, her residual risk to be a carrier of cystic fibrosis is about 3 percent.
  • If Mary did not have any family history of cystic fibrosis, her likelihood to carry a variant in CFTR would be reduced to less than 1 in 200 or less than 0.5 percent with normal carrier testing.