Information For Participants
What is the Goal of NCGENES?
The goal of NCGENES is to learn if a new technology, “next-generation sequencing”, is ready to be used in routine medical care. It will be used for a new genomic test called Whole Exome Sequencing (WES).
What is Whole Exome Sequencing?
Whole Exome Sequencing (WES) is way to figure out the sequence (the order of the DNA bases) of the exons of the genes while ignoring the rest of the DNA in the genome. An exon is the part of the gene that carries the code for the creation of proteins. WES can potentially look at the exons of all the genes at the same time.
Everyone has the same set of ~20,000–25,000 genes. When the exomes of two unrelated people are compared, many differences in the DNA sequences will be found between them. These differences are called variants. Variants can have beneficial effects, harmful effects or no effects. When a person’s health problems result from genetic variants, sequencing may identify them. Genetic variants may explain a person’s medical problems and help guide doctors, patients and families in making medical decisions.
What Kinds of Information Might I Learn After Having WES?
WES might find genetic variants that provide information about the health concern that made you eligible for this study. This diagnostic information may help your doctor in treating your symptoms.
There are 3 categories of diagnostic results:
- Positive result: a genetic variant is identified in a gene associated with a genetic disorder that explains your personal and/or family history.
- Uncertain result: a genetic variant is identified in a gene associated with a genetic disorder that may explain your personal and/or family history but its clinical meaning is uncertain.
- Negative result: no potentially causative variant has been identified that explains your personal and/or family history in the subset of genes that was studied.
WES could find genetic variants that are not related to your diagnosis. This is called incidental information. There are 3 types of incidental information: medically actionable, non-medically actionable, and no known medical significance.
Medically actionable incidental information:
In some very rare cases, a genetic variant might be found that suggests that you currently have a serious medical condition that can be treated OR that you are at high risk for a future medical problem that can likely be prevented. This is called medically actionable incidental information. It is very unlikely that your WES will find this type of information. However, if it does, you will be told about it.
Non-medically actionable incidental information:
Most incidental information will not help you or your doctor plan your health care. This type is called non-medically actionable incidental information. For example, it can provide information about conditions or risks that are not currently preventable or about risks for future generations. Some types may be of interest to some people but not to others. Some types might cause distress to some people but not to others.
One goal of NCGENES is to find out whether people want to know this information, how they understand it, how they use it, and its impact on them. To study these questions, adult participants will be divided randomly into two groups.
Group 1: participants will learn diagnostic and medically actionable incidental results.
Group 2: participant will learn diagnostic and medically actionable incidental results but will also be asked to consider whether or not they want to learn non-medically actionable incidental information. Participants in this group will be given more information later.
No known medical significance:
The overwhelming majority of genetic variants have no known medical significance. These variants will not be interpreted or reported to you as part of the NCGENES study.
What Will I Be Asked To Do?
To join the study, you will come to UNC for the first study visit to learn more about WES and to provide a blood sample. The visit will last about 1 hour. In about 3-4 months, you will return for a second, hour-long visit to discuss the information learned from your WES.
Between visits, you will be called and asked survey questions that will take about 45 minutes. You will also complete a paper questionnaire at home that will take about 20 minutes. After the second visit, you will complete a second telephone survey and second questionnaire. During the next 6 months, you will complete a third and fourth telephone survey.