Associations between self-referral and health behavior responses to genetic risk information

Background Studies examining whether genetic risk information about common, complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results. Examining the influence of different study recruitment strategies may help reconcile inconsistencies. Methods Secondary analyses were conducted on data from the REVEAL study, a series of randomized clinical trials examining the impact of genetic susceptibility testing for Alzheimer’s disease (AD). We tested whether self-referred participants (SRPs) were more likely than actively recruited participants (ARPs) to report health behavior and advance planning changes after AD risk and APOE genotype disclosure. Results Of 795 participants with known recruitment status, 546 (69%) were self-referred and 249 (31%) had been actively recruited. SRPs were younger, less likely to identify as African American, had higher household incomes, and were more attentive to AD than ARPs (all P < 0.01). They also dropped out of the study before genetic risk disclosure less frequently (26% versus 41%, P < 0.001). Cohorts did not differ in their likelihood of reporting a change to at least one health behavior 6 weeks and 12 months after genetic risk disclosure, nor in intentions to change at least one behavior in the future. However, interaction effects were observed where ε4-positive SRPs were more likely than ε4-negative SRPs to report changes specifically to mental activities (38% vs 19%, p < 0.001) and diets (21% vs 12%, p = 0.016) six weeks post-disclosure, whereas differences between ε4-positive and ε4-negative ARPs were not evident for mental activities (15% vs 21%, p = 0.413) or diets (8% versus 16%, P = 0.190). Similarly, ε4-positive participants were more likely than ε4-negative participants to report intentions to change long-term care insurance among SRPs (20% vs 5%, p < 0.001), but not ARPs (5% versus 9%, P = 0.365). Conclusions Individuals who proactively seek AD genetic risk assessment are more likely to undergo testing and use results to inform behavior changes than those who respond to genetic testing offers. These results demonstrate how the behavioral impact of genetic risk information may vary according to the models by which services are provided, and suggest that how participants are recruited into translational genomics research can influence findings. Trial registration ClinicalTrials.gov NCT00089882 and NCT00462917 Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0124-0) contains supplementary material, which is available to authorized users.


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There are three different forms of the APOE gene-E2, E3, and E4.

Alzheimer's Disease and the APOE Gene
Inheriting a specfic form of the APOE gene can increase the risk of getting Alzheimer's disease. The role of the APOE gene in Alzheimer's disease is still being studied. Some studies have shown that it may be related to other conditions in addition to Alzheimer's disease.
We do know that the APOE gene comes in three different forms: E2, E3, and E4. Every person has two copies of the APOE gene-one inherited from each parent. Because there are three different forms of the APOE gene and there are two APOE genes in every person, an individual posesses one of six unique APOE combinations (pictured below).
If an individual has one or two copies of the E4 form of the APOE gene, it increases his or her risk of developing Alzheimer's disease. However, this does not mean that he or she will definitely get Alzheimer's disease.

APOE Genetic Testing
As part of your risk assessment, we provide APOE testing. There are three basic steps to APOE testing. First, you will meet with a genetic counselor to review any questions or concerns about having an Alzheimer's disease risk assessment, including APOE testing. Next, you will provide a small blood sample for APOE testing. Finally, you will meet with a clinician to learn and discuss your test result and risk assessment. Test results are typically available within a few weeks of the blood draw.

E4
You will be given an estimate of your risk of developing Alzheimer's disease by the time you are 85 years old. Depending on your risk factors, you will be given a risk number between approximately 15% to 75%. Your risk estimate will also be shown on a graph, similar to that pictured below.

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There are six possible combinations of the three APOE forms. These combinations are called genotypes.
The characteristics taken into account in the risk assessment include your age, gender, race, APOE test result, and whether or not you have a parent, brother, or sister with Alzheimer's disease.
We are still learning about many other genetic and nongenetic factors that are involved in the development of Alzheimer's disease. As scientists learn more about what causes Alzheimer's disease, this new information may alter your risk assessment.

Issues to Consider
You may want to consider several issues before having a risk assessment for Alzheimer's disease. Your risk profile is only an interpretation based on our current knowledge and will not give you a simple "yes" or "no" answer, nor will it indicate at what age Alzheimer's disease may develop.
There are no proven ways to prevent Alzheimer's disease from developing.

Resources
Contact the following organizations to learn more about Alzheimer's disease.

Understanding Your Risk of Alzheimer's Disease
Alzheimer's disease is a brain disease that is the most common cause of memory and language problems in older people. It can impair a person's ability to carry out daily activities. Although we are learning more about the cause of the disease, and treatments are available for some of its symptoms, there is currently no cure or prevention for Alzheimer's disease. An estimated 5 million Americans have Alzheimer's disease -a number that is projected to grow to over 13 million by 2050. The general population's lifetime risk of developing Alzheimer's disease is about 12%.

Alzheimer's Disease and the APOE Gene
Inheriting a specific form of the APOE gene can increase the risk of getting Alzheimer's disease. The APOE gene's specific role in Alzheimer's disease is still being studied. Some studies have shown that it may be related to other conditions in addition to Alzheimer's disease.
We do know that the APOE gene comes in three different forms: e2, e3, and e4.
Every person has two copies of the APOE gene-one inherited from each parent.
Thus, an individual can have one of six possible combinations of the APOE gene (pictured below).
An individual who carries one or two copies of the e4 form of the APOE gene is at increased risk of developing Alzheimer's disease.

Factors to Consider
You may want to consider several factors before having a risk assessment for Alzheimer's disease. Certain limitations are inherent in the process. Your risk profile is an interpretation based on our current knowledge and will not give you a simple "yes" or "no" answer, nor will