Ethical Issues of Genetic Testing in Schizophrenia
Ethical Issues of Genetic Testing in Schizophrenia
Should incidental findings be shared with consumers? Whole genome sequencing leads to a large accumulation of data. Despite companies producing some filtration of the data to be able to communicate a concise single page report with clinical usefulness, incidental findings (those that have not been requested) can appear in reports. If one orders a screen for one disease, that is schizophrenia, should the company be obligated to inform the individual that they also have the proven risk factors for other diseases such as breast cancer or Alzheimer's if he/she did not request it? Controversy continues about what should be done with these findings. Does the consumer have a right, regardless of what it is, to know all the details within the context of one's own genome or a right not to know? The American College of Medical Genetics has released recommendations for 24 conditions that should systematically be disclosed to the patient. At this stage, these are the only clinically useful ones that can lead to benefit to the patient, and thus the only 'incidental' findings that should be communicated. They do not include genetic risk variation for schizophrenia.
Research on incidental findings is currently a priority focus of the Ethical, Legal and Social Implications Research Program of the National Human Genome Research Institute (http://www.genome.gov/10001618). Two hundred thirty-four researchers of the US genetic research community completed an online questionnaire, and 28 an extensive semistructured interview to understand their views of and experiences with incidental genetic research findings. Ninety-five percent of respondents would disclose information about highly penetrant, actionable findings; over 60% would disclose information on highly penetrant alleles even if no intervention is available; 80% would disclose information on modestly penetrant alleles with available interventions; and 16% would prefer to disclose a list of variants from the entire genome.
Should a child have a right to choose such a test when he/she is within the age of risk for the illness? Some believe that if there is no clear premorbid treatment, there is no clinical benefit, and thus informing the child is not ethically sound. On the contrary, if the child is symptomatic in a prodromal stage, one might think sharing this risk would be helpful. The danger is of false negatives, and thus a false sense of confidence that medication and other preventive measures may not be necessary.
The clearest, yet rare, DNA risk factors that may be worth screening for to date are CNVs that have been shown to be associated with schizophrenia, such as the deletion in 22q11.21 that confers an approximately 68% risk of schizophrenia on people who have it. Although one would not put much value in tests with effect sizes too small for clinical utility, in the future aggregate risk factors for a polygenetic component may become usable in genetic counseling, although the ethical use of these factors needs to be considered, such as whether either pregnancy planning or pregnancy termination should be considered based on parental or antenatal genetic risk profiling or even preimplantation in-vitro selection of embryos.
If an individual is known to be carrying a risk factor for a Mendelian disorder, there may be an issue as to whether it is one's duty to inform siblings and other close relatives. It is much less clear for risk factors for schizophrenia, as, while CNVs could be highly penetrant, they also could have arisen de novo and not have been passed on from a parent, thus suggesting that other relatives may not be at high risk.
One can foresee that in the future, should genetic testing become commonplace, prospective mates will request DNA results. In previous decades, syphilis testing was a requirement in many states before marriages could be performed, and currently AIDS screening would not be an unreasonable request to a prospective partner. Where DNA screening differs is that one is then no longer concerned about jeopardizing one's own health, but rather that of a child that is conceived in the future. Regardless, it is clear that public ethical debates about DNA testing have not yet reached the forefront of the medical industry worldwide and that, until they do, testing will occur without knowledge of how much damage or good it has done.
Any psychiatric geneticist who attended the WCPG in 1998 in Bonn, Germany, may recall an excursion that was made during the midpoint of the congress to a psychiatric facility, named Hadamar, just outside Frankfurt. It was there that thousands of patients with schizophrenia, as identified by their psychiatrists, were 'euthanized' in the mistaken belief this could help terminate new generations of offspring who had inherited the illness. Ethical issues aside, there was clearly a severe lack of understanding of the genetic research findings and how they could be put to practical use in the clinic. The gap in knowledge between what geneticists should have known, and public/political interests, was tremendous. Similarly, the unchecked growth in commercial testing is occurring with a lack of regulations and lack of informed consent by consumers, and the gap in knowledge between groups must be tremendous. Public discussion has not yet addressed the issue of stigma, and thus discrimination, because of one's genetic constitution. One can imagine that if these genetic reports go unregulated, the future may bring the need for disclosure of someone's DNA when applying for jobs, and certainly those with risk factors for mental illness or dementia would be eliminated from the applicant pool. Insurance policies may be higher-priced or even denied to people whose DNA shows elevated risk for mental illness. There are several other discriminatory practices that could occur.
Should providing public education for placing the real risks in perspective be the responsibility of the researchers who uncovered the risks, or should it be in the hands of government regulators, rather than simply allowing genetic testing to become pervasive as dictated by commercial advertising and appeal? Certainly, open discussion and education between all groups involved would be helpful to understand the ethical and social uses of the information gained from psychiatric genetic research, as well as its limitations.
Ethical Issues Without Resolution
Incidental Findings
Should incidental findings be shared with consumers? Whole genome sequencing leads to a large accumulation of data. Despite companies producing some filtration of the data to be able to communicate a concise single page report with clinical usefulness, incidental findings (those that have not been requested) can appear in reports. If one orders a screen for one disease, that is schizophrenia, should the company be obligated to inform the individual that they also have the proven risk factors for other diseases such as breast cancer or Alzheimer's if he/she did not request it? Controversy continues about what should be done with these findings. Does the consumer have a right, regardless of what it is, to know all the details within the context of one's own genome or a right not to know? The American College of Medical Genetics has released recommendations for 24 conditions that should systematically be disclosed to the patient. At this stage, these are the only clinically useful ones that can lead to benefit to the patient, and thus the only 'incidental' findings that should be communicated. They do not include genetic risk variation for schizophrenia.
Research on incidental findings is currently a priority focus of the Ethical, Legal and Social Implications Research Program of the National Human Genome Research Institute (http://www.genome.gov/10001618). Two hundred thirty-four researchers of the US genetic research community completed an online questionnaire, and 28 an extensive semistructured interview to understand their views of and experiences with incidental genetic research findings. Ninety-five percent of respondents would disclose information about highly penetrant, actionable findings; over 60% would disclose information on highly penetrant alleles even if no intervention is available; 80% would disclose information on modestly penetrant alleles with available interventions; and 16% would prefer to disclose a list of variants from the entire genome.
Should a Child Be Tested for Risk of Schizophrenia?
Should a child have a right to choose such a test when he/she is within the age of risk for the illness? Some believe that if there is no clear premorbid treatment, there is no clinical benefit, and thus informing the child is not ethically sound. On the contrary, if the child is symptomatic in a prodromal stage, one might think sharing this risk would be helpful. The danger is of false negatives, and thus a false sense of confidence that medication and other preventive measures may not be necessary.
Should Risk of Schizophrenia Be Considered in Antenatal or Prenatal Screening?
The clearest, yet rare, DNA risk factors that may be worth screening for to date are CNVs that have been shown to be associated with schizophrenia, such as the deletion in 22q11.21 that confers an approximately 68% risk of schizophrenia on people who have it. Although one would not put much value in tests with effect sizes too small for clinical utility, in the future aggregate risk factors for a polygenetic component may become usable in genetic counseling, although the ethical use of these factors needs to be considered, such as whether either pregnancy planning or pregnancy termination should be considered based on parental or antenatal genetic risk profiling or even preimplantation in-vitro selection of embryos.
Should Family Members Have the Right to Know Risk to Other Relatives?
If an individual is known to be carrying a risk factor for a Mendelian disorder, there may be an issue as to whether it is one's duty to inform siblings and other close relatives. It is much less clear for risk factors for schizophrenia, as, while CNVs could be highly penetrant, they also could have arisen de novo and not have been passed on from a parent, thus suggesting that other relatives may not be at high risk.
Will Genetic Testing Have a Role in Marital Choices?
One can foresee that in the future, should genetic testing become commonplace, prospective mates will request DNA results. In previous decades, syphilis testing was a requirement in many states before marriages could be performed, and currently AIDS screening would not be an unreasonable request to a prospective partner. Where DNA screening differs is that one is then no longer concerned about jeopardizing one's own health, but rather that of a child that is conceived in the future. Regardless, it is clear that public ethical debates about DNA testing have not yet reached the forefront of the medical industry worldwide and that, until they do, testing will occur without knowledge of how much damage or good it has done.
Danger of Misused Genetic Information
Any psychiatric geneticist who attended the WCPG in 1998 in Bonn, Germany, may recall an excursion that was made during the midpoint of the congress to a psychiatric facility, named Hadamar, just outside Frankfurt. It was there that thousands of patients with schizophrenia, as identified by their psychiatrists, were 'euthanized' in the mistaken belief this could help terminate new generations of offspring who had inherited the illness. Ethical issues aside, there was clearly a severe lack of understanding of the genetic research findings and how they could be put to practical use in the clinic. The gap in knowledge between what geneticists should have known, and public/political interests, was tremendous. Similarly, the unchecked growth in commercial testing is occurring with a lack of regulations and lack of informed consent by consumers, and the gap in knowledge between groups must be tremendous. Public discussion has not yet addressed the issue of stigma, and thus discrimination, because of one's genetic constitution. One can imagine that if these genetic reports go unregulated, the future may bring the need for disclosure of someone's DNA when applying for jobs, and certainly those with risk factors for mental illness or dementia would be eliminated from the applicant pool. Insurance policies may be higher-priced or even denied to people whose DNA shows elevated risk for mental illness. There are several other discriminatory practices that could occur.
Who Should Be Educating the Public?
Should providing public education for placing the real risks in perspective be the responsibility of the researchers who uncovered the risks, or should it be in the hands of government regulators, rather than simply allowing genetic testing to become pervasive as dictated by commercial advertising and appeal? Certainly, open discussion and education between all groups involved would be helpful to understand the ethical and social uses of the information gained from psychiatric genetic research, as well as its limitations.
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