After being asked if they wanted to be informed about a specific genetic variant, should they be found to be a carrier, 17 participants wanted to be alerted about the variants BRCA1 and BRCA2, while 3 declined. In the event of mutations in the parkin gene, 7 individuals expressed the desire to be notified, 10 decided against it, and 3 remained undecided. Nine participants asked for disclosure of the variant causing Huntington disease, while 11 did not wish to learn about it.
During two interviews, in which the participants did not want to be informed about any of the three presented genetic variants, the interviewers decided to present MH as an additional example. Both participants stated that they wanted to be notified if they had the variant related to MH.
In one interview, a participant stated that they did not want to be informed about variants related to Parkinson disease, as they had personal experience with the disease. The participant also did state that they would not want to be informed about any variant with potentially severe health implications, no matter the variant’s other characteristics. Following this, the interviewers decided to present the example of the restless legs syndrome (RLS), as it has similar characteristics to Parkinson disease (no, preventative measures, no cure) but with less severe health consequences. The participant wanted to be informed about RLS.
Disclosure—an intrinsic decision
The choices made by participants and the motivations behind them proved to be extremely diverse and highly personal. A common observation, however, was that participants wanted to make an autonomous decision regarding the disclosure or non-disclosure of their results. Some stated that they would feel betrayed or disappointed if results were available but not offered to them. Several participants felt that they have a right to be informed about available personal genetic results, even if it might be categorized irrelevant by researchers or genetic specialists. Participants felt that decisions on disclosure of results must remain with the individual and that these preferences may change over time in accordance with their own preferences and changes in scientific knowledge.
Some participants allocated a clear responsibility to the study to inform and help study participants and therefore share results. However, some stated that the CHRIS study should serve the common good and therefore would understand if no results are offered due to economic limitations.
Decision factors for disclosure
Although factors affecting decision were highly personal, there were some common criteria. They were actionability of results, disease factors, and impact on genetic relatives.
Actionability of results
The medical actionability of genetic results played a central role in participants’ decisions on disclosure. Participants were presented and discussed four subcategories of actionability:
The possibility to entirely prevent the onset of a disease;
The possibility to recover completely after the onset of a disease which cannot be prevented;
The availability of precautionary measures that cannot prevent the outbreak of a disease but facilitate early recognition and timely treatment and potentially cure;
The availability of medical treatment or lifestyle changes that cannot cure the disease but delay its progress or ease its symptoms.
Fear of experiencing anxiety was a cross-cutting argument against disclosure of results of all categories, while the key argument for disclosure was the possibility to take actions and the feeling of being prepared for the future. Participants weighed these factors against each other in their decisions and made very diverse choices.
Possibility to prevent onset of a disease
All participants wanted to be informed about results that could facilitate the complete prevention of the onset of an illness. These results were seen as a unique opportunity to take active measures to stay healthy and the probability to suffer from anxiety was evaluated as low.
Possibility to cure a disease
Genetic variants that increase the risk of developing a disease which can be cured once it breaks out, but not prevented beforehand, led to diverse decisions on disclosure. Participants deciding for disclosure reasoned that because the disease was curable, they would not worry, but be able to inform themselves early on about risks and treatment options.
[…] you will be more attentive, if something is out of the ordinary. That you rather say, now I will let this be checked or so… Or otherwise maybe… ahm you will not pay attention to it and then it might be too late. (Participant 02).
Other participants saw no advantage in knowing these genetic predispositions because they cannot take any proactive measures before any symptoms show. They feared burdening their lives with unnecessary anxiety as the disease might never break out, and if it did, they would still be able to undergo medical treatment and cure the disease.
No, I would not want that. As soon as it occurs, I will have to handle it, but I don’t want to know. […] Because maybe then in my fear…. I would live in fear it could be affected or I could get this disease and that I do not want because I still cannot do anything against it. (Participant 01).
Availability of precautionary measures to treat or cure
Where results would enable participants to take precautionary measures that cannot prevent the disorder but lead to early detection and treatment, a number of participants stated that knowing their results would motivate them to take precautionary measures or have regular medical check-ups. The possibility to act before a disease might break out as well as the fear of missing the chance of intervening early enough led participants to decide for disclosure.
[…] If you know that, you might be more diligent with the check-ups. Otherwise you always think: ahh not me, or, yes yes I will do that sometime, or … exactly and I think if you know you are in this thing, that it could be…, I think you will be more diligent with the check-ups. You will say, yes ok now I will do this once a year. (Participant 02).
Others, however, feared they would burden their lives with stressful medical visits that will not be able to prevent the development of the disease. These participants felt that concerns on the suffering of anxiety outweighed the benefit of the limited actions available.
I would not make the test, because if I get it, I get it (breast cancer), and I don’t care if I have a higher risk or not. […] I would not … how do you say … visit the doctor more frequently, because I have it (genetic variant). I would not do it. (Participant 9).
All participants expected that results for diseases that can be eased through medical interventions but not completely cured will cause worries. However, some regarded the possibility to mentally prepare themselves for the consequences of a disorder as more valuable. They expected that the availability of medical treatment options would ease their worries and led them to decide for disclosure. One participant also explicitly stated that if traditional medicine cannot provide a cure, they would search for treatment or prevention options from alternative medical schools like traditional Chinese medicine.
… there are maybe people that, let’s say, sleep away, their life. And I think if someone has something like this (Huntington disease), then he can prepare himself. Also things like arrange things at home, like the last will, because I think later you cannot do this anymore. And things like that. Yes, I think that is important (Participant 11).
Other participants felt that since no actions can be taken to prevent or cure the disease, knowing their genetic predisposition was pointless. They feared such results would cause anxiety and thus lower their life quality. Moreover, they also expressed the concern that knowing their results might alter important decisions in their lives.
The difference is, you cannot do anything against it, it does not matter if I know it sooner or later, it is here when it is here. And because you cannot do much, I do not think it is like breast cancer, that is something else. Because there I can really say if I know it early on I can… I have a bigger chance to be cured. That is the difference yes. (Participant 5).
The characteristics of the genetic variant were especially important for participants’ decision on disclosure, namely, the risk or probability of actually developing a disease, the severity of the disease, the age in which the disease is most likely to develop, and the availability of alternative ways of diagnosis besides genetic testing.
The probability of developing a genetic disorder due to a certain genetic variant was relevant results that participants requested in order to make their decision on disclosure. The mutations in the parkin gene represent a very low risk of developing the Parkinson disease while the example of Huntington disease represented a high risk, as a mutation in the Huntingtin gene will always lead to the manifestation of the disease.
Participants who decided for disclosure of a low risk level result stated that they wanted to know any genetic results on their health, as it might be useful in the future.
Yes… I want to know everything, if that is possible. Even if it is not sure, that it will develop, but…yes. (Participant 14).
The main motivation for those wanting to know high risk level results was the desire to be able to plan their future and take the disease into account when making important life decisions. While some considered not working as hard as they do, others would rethink their family planning.
… I want to know it. In general, if I would have… so I can organize my life until it actually breaks out or first symptoms show. […] Yes, so I can still plan my life. Like go on holydays sometime and travel. Otherwise I always postpone it and like this I could go sooner. (Participant 15).
Some participants argued that a high risk combined with the absence of medical interventions would be a motivation against disclosure. They felt a result like this would prevent them from living a full life in the present as constant worries for the future would prevail.
Closely connected to risk level is the severity of a disease related to a certain genetic variant. Here, participants differentiated between mild diseases that have a low impact on the utilization of resources, comorbidities, and mortality and severe diseases that have a high impact. Those asking for disclosure for results connected to mild diseases argued that they did not expect to suffer from anxiety upon learning of such results. Instead, they valued the opportunity to inform themselves about the disease and mentally prepare themselves before a potential outbreak.
Yes. You will always have a little bit of fear as well. But you may be able to do something if it breaks out, maybe you can alleviate it. (Participant 17).
Similarly, those asking for disclosure of results for a severe disease evaluated the chance to know their risk of developing a disease that might have a great impact on their life as favorable, because they wanted to be able to plan their life accordingly.
But yes… so you can take provisions and I think the earlier the better. You can also prepare mentally somehow… (Participant 11).
Participants opting against disclosure for mild diseases as well as those deciding against results relating to severe diseases stated that they feared knowing their results would lead to anxiety. While the anxiety caused by variants related to mild diseases was evaluated as unnecessary since the disease will have relatively minor consequences for their lives, participants feared that the worries caused by severe diseases would affect their life choices in a negative way.
That you maybe will already fixate on it too much. Also I think you maybe already feel a tremor even if there is none. That is a shame if you already worry too early about something that probably or maybe will never come. (Participant 5).
Age of onset
The age of onset of a disorder related to a genetic variant proved to be an influential factor for participants’ decision. Generally, participants rather wanted to be informed about diseases with an early onset. Illnesses that are estimated to only develop after the age of 60 were considered less relevant. However, participants expected that their preference will change over time and with advancing age.
(…) one should always be able to change one’s mind. […] Because one will maybe be more adult and then one might have a different opinion. (Participant 9).
Some participants above the age of 60 indicated that they did not want to know any genetic results, even if the consequences of a genetic mutation might affect them soon. They argued that genetic results are no longer relevant for them, but they participated mainly for the benefit of their descendants.
(…)Yes for my descendants. Because for myself it is not that important… let’s say it is important, but it does not benefit me anymore. The clinical exams yes, but the research results are for my descendants. (Participant 3).
Chances for diagnosis
Another interesting factor that emerged from the interviews was the question concerning alternative possibilities for diagnosis. If obtaining the genetic results from the CHRIS study was the only chance for participants to receive a diagnosis, some wanted to be informed about results that had characteristics that would normally lead them to reject disclosure. The same applied also if getting a diagnosis would be possible but potentially very difficult or require invasive testing.
If there is no other way of identifying the disease, I would like to know. Otherwise not. (Participant 5).
Impact on genetic relatives
Another important decision factor was the significance of genetic results for participants’ children and relatives.
The heritability of a genetic defect greatly influenced the decision of participants that already had or planned to have children. Many participants wishing to have children in the future wanted to know their risk, as they did not want to pass on any disease to their children and would consider pursuing alternative family planning options.
Well then I would wonder if I even want to have children, because it is an imposition. The children cannot decide if they want to have the gene. I think it is a little bit selfish if you then just… just make this decision for the children. (Participant 10).
Others, however, did not want that a mere risk to influence such an important life decision. Several participants demanded specifically not to be informed, as it might generate anxiety in their children or because they felt their children had the right to decide themselves if they wanted to know such results once they are grown up.
No. Even if the kids are… (affected). I already have two children so… […]. I do not want to know that, no. Because there you see no chance somehow, that this can’t be or so. (Participant 04).
The prospect that other relatives might be affected by a genetic mutation was evaluated as a less decisive factor as the possibility of passing it onto their children. Many participants felt that their relatives had to decide for themselves if they wanted to take genetic examinations and expressed uncertainty as to whether they would share their results with their family. However, certain participants that had experiences with severe diseases in their family reported it would be important to share any results to enable their relatives to take appropriate action.
Participants’ misconceptions about genetic results in CHRIS
Throughout the interviews, two major misconceptions regarding the return of unsolicited results in the CHRIS study were identified.
Firstly, during the informed consent process of the CHIRS study, participants were informed that researchers are not actively searching for diagnostic variants. This fact was explicitly mentioned in the participant brochure, in the introductory video to the CHRIS study that all participants viewed prior to participating in the study, and in the consent form. It was also stated that in rare cases in which relevant results were identified during research, participants will be contacted according to their preferences indicated on the consent form. Despite this, many participants assumed that the researchers would actively look through their data to identify genetic variants that might lead to the development of a disease and they expected to be contacted in case relevant results were available. This led participants to presume that if the CHRIS study did not contact them, no relevant genetic mutations had been detected during the active screening.
Secondly, it was detected that while people were aware of the possibility to receive genetic results or even expected it, there was limited understanding as to the meaning of genetic results. During the interviews, participants expressed surprise when the three examples of genetic variants and their health implications were presented to them. Participants stated that they were unsure of what genetic results are and that they were unaware of the broad range of possible results in terms of risk, the severity of potential health implication, and treatment possibilities.
The results from the questionnaire demonstrated that participants have an average knowledge of genetics. Participants had to rate 9 statements on inheritance and the development of genetic diseases true or false. In sum, participants answered 105 of 180 questions correctly and 44 incorrectly and 31 questions remained unanswered. Regarding their self-evaluation, 9 participants evaluated their knowledge on genetics as very low and 5 as low and 6 indicated to know a bit. None of the participants self-reported as having a good or very good knowledge. Also, in the questionnaire, the participants expressed the feeling that their level of knowledge is either equal to the general public or lower. The high number of unanswered questions from the questionnaire and the low self-evaluation indicate that participants have a basic knowledge on genetics.
The opinion and role of general practitioners and the genetic counsellor in ROR
All GPs supported the return of genetic results as being useful and a right of the participants but they also voiced several concerns. They were especially worried that genetic results might create fear and anxiety among their patients. Further, they were concerned that patients would misinterpret genetic results as a clinical diagnosis. They expressed concern on how participants might react, when learning about their elevated risk to develop certain diseases. They argued that as the general population has no experience in receiving and interpreting genetic results, they might be overwhelmed and over-interpret their predispositions. This might lead them to take unnecessary medical interventions. They emphasized that research results must be clinically validated before returning them.
At the moment I think so because the awareness of how to deal with such results is not very widespread yet. I think this will rather have a shocking effect… (General Practitioner 3).
Another concern voiced was that the genetic results about a person or a family being affected by genetic disorder might spread around the villages and cause social stigmatization. Therefore, the GPs stressed the need for utmost discretion when sharing genetic results.
… it is a small country and like I said, news travel fast. And then people are quick to say… oh in this family, they have this and that gen and so on… Honestly, I would be very cautious. Here you can easily stir up a hornet’s nest. (General Practitioner 2).
When confronted with the three examples of genetic results, the GPs had different opinions on what kind of results should be shared. There were particular concerns about genetic variants that only slightly increase the risk of developing a disease, such as the variants described in the example of Parkinson disease. GPs feared that these results might cause unnecessary anxiety among their patients. In general, however, all GPs agreed that the participant should have the right to decide for themselves what kind of results they want to receive.
… The decision has to remain with the proband, with the human. He has to decide. No discussion. […] This is essential. The owner of the genetic data has to decide. Well the patient or the proband has to decide himself. I think we cannot make the decision for him, and we must not. (General Practitioner 1).
Regarding their own role in the returning process, the GPs stated that they did not feel confident to advise their patients on genetic results, as currently genetics plays a minor role in their daily work and they lack the necessary expertise. While the physicians would like to be informed subject to the consent of the participant, about potential genetic results of their patients, they rather see their role in encouraging patients to seek a specialist’s advice or undergo the necessary examination or treatment.
… I am a general practitioner and I have to take care of so many things. If this is getting so detailed, I would refer to the colleagues, the specialists that work in this field. […] Well I see our role in supporting the patients as good as possible and also in encouraging them to take further steps. (General Practitioner 2).
This is in contrast to the views of many participants who reported having a strong personal and trusting relationship with their general practitioners. Some even preferred to be informed about genetic results by their physician instead of a genetic specialist and others demanded that their results would also be sent to their family doctor after a consultation with a specialist.
Rather the general practitioner because you know him better and longer. And also the doctor knows the patient already for a long time. In the hospital it is more anonymous, isn’t it? You are not there often. I would say rather the general practitioner. (Participant 6).
The genetic counselling service in Bolzano supported the return of genetic results to participants and stressed the importance of an autonomous decision on disclosure by the participants that reflects the genetics unit approach to genetic results. They also thought that the cohort could lead to joint projects on several genetic-related disorders that could potentially lead in collaboration with the healthcare system to preventive health projects. For this type of potential development, appropriate understanding and consent of the individuals would be paramount. However, concerns were raised regarding the enormous workload that might arise for their rather small team of only 4 counsellors. The physicians as well as the genetic counselling group stressed that participants cannot be left alone with their results but that a close collaboration between them and the CHRIS study as well as further specialists and psychologists must be built in order to responsibly advise participants.