Genomic Research Result Types
How are genetic variants classified?
In order to return a research result to a participant, a researcher needs to be confident that the identified variant definitely caused the condition in question, or has a very high likelihood of being disease causing. The classification of the variant is based on whether it has been previously reported in association with disease, whether similar variants in the same gene have been reported in association with the participant’s condition, whether the variant segregates with disease (i.e., is present in all affected members of the same family and not present in unaffected family members), whether the frequency of the variant in the general population is consistent with the incidence of the condition, and whether the nature of the variant is predicted to negatively affect protein function.
Universal guidelines are used to classify variants as pathogenic, likely pathogenic, uncertain significance, likely benign and benign (see below). Typically, pathogenic and likely pathogenic variants are reported to participants, though in the case of rare disorders, researchers may also elect to return variants of uncertain significance.
Types of test results which could be returned from a genomics study
-
Some individuals have conditions which are suspected to be genetic, but the diagnosis is uncertain. Identifying the causal gene can confirm a diagnosis and confirm that it is genetic.
-
Identifying the gene causing the condition can also provide information about inheritance, which can provide information about the chances of the participant’s children developing the condition. It can also provide information about the chances that other family members might be affected.
-
Some genes are associated with an increased chance of developing a condition in the future. Knowing this information can sometimes allow for preventative and risk reducing interventions e.g. BRCA1/2.
-
Sometimes an individual will participate in a study in the hopes of identifying the gene which causes their condition e.g., melanoma, but the causal gene also confers a risk for other types of cancer e.g., colorectal cancer or breast cancer. If the person did not have a strong family history of that cancer, this finding would be unexpected.
Primary Findings
Primary findings are results related to the purpose of the research i.e., the reason the participant enrolled in the study. There are many different implications to receiving a primary result:
Secondary Findings
Some clinicians believe that if a person is having genomic sequencing for their primary condition, they should also have the data reanalysed to identify any genetic variants in preventable or treatable conditions. Researchers might offer participants the opportunity to have these additional genes analysed but specific consent must be obtained. These conditions are typically adult onset conditions.
Incidental Findings
A genetic variant is identified in a gene associated with an unrelated condition. This variant was discovered incidentally/inadvertently in the process of analysing the genomic data e.g., researchers looking for the gene for an immune disorder discover that the person is a carrier for haemochromatosis.
Scenario - A girl named Jane
Jane is a young woman who has a heart condition, but prior tests have not revealed the genetic cause. She has decided to participate in a research study with the hope that the causative gene will be identified. During the consenting process, the research genetic counsellor discusses the different types of results which the research might generate.
Please click on the video below.