Prognostication using whole genome and whole exome (WG/WE) sequencing
depends on the use of a tool which - currently - has the potential to add
to rather than decrease uncertainty. A problem in using information from
genomic testing as a prognostic tool is the self-fulfilling nature of
these 'diagnoses'. Many of these will initially be hypotheses, which
become untestable unless the same genotypes are seen in family members or
the variant is reported in the literature. Even where the consequences of
a particular variant are known, a decision to discontinue active care of
an infant is then considered to be an appropriate decision enabled by
genomic methods, yet we will never know what would have happened if the
baby had been supported further - perhaps the variant(s) were not (very)
pathogenic?
The form which non-directive counselling and informed consent would
take in this context remains poorly evidenced. There is a need for
situated empirical research into what constitutes 'informed' consent when
the potential outcomes are so wide ranging. Binary classifications of the
social, legal and ethical challenges into 'pro' versus 'con' lists fail to
recognise that many of the advantages of these technologies are highly
situated, situational and both beneficial and problematic - for example,
increased diagnostic yield is an advantage, but having a diagnosis when
the phenotype is highly variable and not yet apparent means counselling
will be limited in its ability to provide information.
Case 2 raises interesting challenges in that there are Gene x
Environment interactions between copy number variants and adverse fetal,
neonatal and childhood experiences, in terms of increased risk of
psychiatric conditions in later life [1]. The failure to acknowledge the
role of epigenetic factors fails to recognise the complexity of what the
interpretation of prognostic information would/will be. Whilst the
consequences of these complex epigenetic factors are difficult to take
into account, not acknowledging them oversimplifies the situation,
overstating the potential contribution of genomic information in this
context.
Without wanting to invoke genetic exceptionalism, it is difficult to
see how other 'prognostic' investigations, such as MRI, can be compared
with WGS/ES, given the potential for results which impact parents, both in
terms of reproductive decision-making and current and future health. The
extent of the role of genomics requires critical analysis and careful
stewardship, as clinical, ethical, legal and social challenges emerge.
[1] Harold GT et al. Biological and rearing mother influences on
child ADHD symptoms: revisiting the developmental interface between nature
and nurture. Journal of Child Psychology and Psychiatry 2013
Oct;54(10):1038-46. doi: 10.1111/jcpp.12100
Conflict of Interest:
None declared
Prognostication using whole genome and whole exome (WG/WE) sequencing depends on the use of a tool which - currently - has the potential to add to rather than decrease uncertainty. A problem in using information from genomic testing as a prognostic tool is the self-fulfilling nature of these 'diagnoses'. Many of these will initially be hypotheses, which become untestable unless the same genotypes are seen in family members or the variant is reported in the literature. Even where the consequences of a particular variant are known, a decision to discontinue active care of an infant is then considered to be an appropriate decision enabled by genomic methods, yet we will never know what would have happened if the baby had been supported further - perhaps the variant(s) were not (very) pathogenic?
The form which non-directive counselling and informed consent would take in this context remains poorly evidenced. There is a need for situated empirical research into what constitutes 'informed' consent when the potential outcomes are so wide ranging. Binary classifications of the social, legal and ethical challenges into 'pro' versus 'con' lists fail to recognise that many of the advantages of these technologies are highly situated, situational and both beneficial and problematic - for example, increased diagnostic yield is an advantage, but having a diagnosis when the phenotype is highly variable and not yet apparent means counselling will be limited in its ability to provide information.
Case 2 raises interesting challenges in that there are Gene x Environment interactions between copy number variants and adverse fetal, neonatal and childhood experiences, in terms of increased risk of psychiatric conditions in later life [1]. The failure to acknowledge the role of epigenetic factors fails to recognise the complexity of what the interpretation of prognostic information would/will be. Whilst the consequences of these complex epigenetic factors are difficult to take into account, not acknowledging them oversimplifies the situation, overstating the potential contribution of genomic information in this context.
Without wanting to invoke genetic exceptionalism, it is difficult to see how other 'prognostic' investigations, such as MRI, can be compared with WGS/ES, given the potential for results which impact parents, both in terms of reproductive decision-making and current and future health. The extent of the role of genomics requires critical analysis and careful stewardship, as clinical, ethical, legal and social challenges emerge.
[1] Harold GT et al. Biological and rearing mother influences on child ADHD symptoms: revisiting the developmental interface between nature and nurture. Journal of Child Psychology and Psychiatry 2013 Oct;54(10):1038-46. doi: 10.1111/jcpp.12100
Conflict of Interest:
None declared