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Genetics
Published in Cathy Laver-Bradbury, Margaret J.J. Thompson, Christopher Gale, Christine M. Hooper, Child and Adolescent Mental Health, 2021
An alternative approach to using GWAS findings involves investigating the summative risk from combinations of common variants, e.g. polygenic score analysis. Although each individual genetic variant exerts only a small effect, individuals with multiple risk variants are at increased risk of developing psychiatric disorders. At present, polygenic risk scores are only weakly predictive for psychiatric disorder and cannot be used for clinical testing. Nevertheless, studies that utilise composite measures of genetic risk have yielded important insights about the nature of psychiatric disorder. For example, it has been shown that many psychiatric disorders lie at the end of a population continuum, rather like hypertension lying at the extreme of blood pressure (Taylor et al., 2019).
Smart People / Cognitive Enhancement
Published in Jonathan Anomaly, Creating Future People, 2020
If we can assign polygenic scores to quantify the likelihood that an embryo will develop specific cognitive styles, or personality traits, parents will face hard choices. Some of these choices may involve moral dilemmas, but many will simply be a matter of personal taste. For example, evidence indicates that people who score high on conscientiousness and agreeableness tend to be good friends and co-workers, in part because they pay attention to and act on the needs of others, and because they delay gratification in the pursuit of plans (Nettle, 2006). But being agreeable makes you more likely to get taken advantage of by others, and conscientious people who are motivated to efficiently pursue goals may be considered less fun to be around by those who just want to relax.
Will Systems Biology Transform Clinical Decision Support?
Published in Paul Cerrato, John Halamka, Reinventing Clinical Decision Support, 2020
The Institute for Systems Biology, for instance, conducted a study—the P100 Wellness Project—that enrolled over 100 individuals for 9 months and monitored their health with Fitbit devices, genome sequencing, clinical tests, and analysis of their metabolomes, proteomes, and microbiomes.24 Their detailed analysis uncovered important patterns, relationships, and biomarkers that may be of value in tracking health and disease. Gamma-glutamyltyrosine, a metabolite of the enzyme gamma-glutamyl transferase, was interconnected with clinical analytes associated with cardiometabolic disease. Although the enzyme is a known marker for liver disease, diabetes, and cardiovascular risk, the metabolite is more predictive than the enzyme and may be useful as an independent marker, if these results can be confirmed by larger studies. Their data collection also allowed investigators to develop polygenic scores, based on GWAS, for 127 traits and diseases. Among the many findings, “genetic risk for inflammatory bowel disease was negatively correlated with plasma cystine.”24
Nurtured Genetics: Prenatal Testing and the Anchoring of Genetic Expectancies
Published in The American Journal of Bioethics, 2023
Rémy Furrer, Shai Carmi, Todd Lencz, Gabriel Lázaro-Muñoz
Due to advances in personalized genomics, it has become possible to quantify genetic variance and use it as an individual source of information. Polygenic Scores (PGS) are probabilistic scores that can provide information about an individual’s genetic likelihood of developing any (conceivably measurable) phenotypic trait. (i.e., extraversion, intelligence, height…etc.). Not only is genetic variance quantifiable and accessible as a source of information, but it can also precede most sources of environmental variance through prenatal testing. That is, parents can receive probabilistic genetic scores as the very first piece of evaluative information about their child. This genetic information will precede any (observable) environmental influences on their child’s development, and it is upon these initial probabilistic genetic estimates that they will create expectancies as to who their child will become and how they will behave. The concern is that polygenic scores—which only account for a relatively small portion of individual behavioral variability (see Plomin and Von Stumm 2022 for recent PGS estimates)—will lead parents to over-value genetic information over subsequent environmental information in forming an initial impression of their child.
Non-Invasive Prenatal Testing for “Non-Medical” Traits: Ensuring Consistency in Ethical Decision-Making
Published in The American Journal of Bioethics, 2023
Hilary Bowman-Smart, Christopher Gyngell, Cara Mand, David J. Amor, Martin B. Delatycki, Julian Savulescu
It is important to note that the utilization of polygenic scores to predict a variety of traits is currently of limited use for a variety of reasons that will be explored (Duncan et al. 2019; Martin et al. 2019). Although proponents of the use of polygenic scores emphasize their potential, it may be the case that even with further research, they are ultimately not useful in reproductive decision-making. Nonetheless, it is important to assess the ethical issues associated with emerging technologies before they become possible, even if some of these technologies do not mature. It is also important to note that these technologies may come into use even if they remain relatively unreliable, particularly in the DTC sector, if there is consumer demand for such a test and companies oversell test performance.
Terminology and Consistency
Published in The American Journal of Bioethics, 2023
A third question of terminology relates to “prediction.” Polygenic tests are presented by Bowman-Smart et al as plausibly giving us predictive information: “It may also be possible to use polygenic scores … to predict a variety of non-medical traits such as cognitive ability …” While a quiet note of caution is introduced later, the damage has been done as polygenic scores and prediction are immiscible: these terms simply do not mix. Polygenic scores give information that might modify a prior risk estimate but that is all. They may conceivably have some clinical utility in setting criteria for screening or surveillance programs, although none have so far been established. Equating polygenic scores with prediction amounts to the implicit promotion of a false genetic determinism, while leaving aside the problems of pleiotropy, complexity and inequity they acknowledge (Turley et al. 2021). Furthermore, the focus on cognitive ability lends unwise support to the persistent—historical and contemporary—over-emphasis on variation in IQ within the normal range that is of no relevance to medicine but is wide-open to abuse.