Concerns about the use of polygenic embryo screening for psychiatric and cognitive traits

Lencz, Todd; Sabatello, Maya; Docherty, Anna R.; Peterson, Roseann E.; Soda, Takahiro; Austin, Jehannine; Bierut, Laura J.; Crepaz‐Keay, David; Curtis, David; Degenhardt, Franziska; Huckins, Laura; Lázaro‐Muñoz, Gabriel; Mattheisen, Manuel; Meiser, Bettina; Peay, Holly; Rietschel, Marcella; Walss‐Bass, Consuelo; Davis, Lea K.

doi:10.1016/s2215-0366(22)00157-2

Cited by 17 publications

(6 citation statements)

References 78 publications

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“…The couple then used a third-party service to compute PRS for schizophrenia and intelligence and selected their embryo based on these scores. Not only does this raise major ethical concerns given the association with eugenics and ableism, but the fact that the PRS for schizophrenia is associated with positive traits such as increased openness to new experiences 195 and creativity 196 emphasizes that selection based on tools with limited predictive ability for traits which are still poorly understood and subject to stigma and discrimination could result in unintended and unwanted consequences [282][283][284] . Researchers affiliated with Genomic Prediction Inc. have since constructed a polygenic health index by combining PRS for 20 impactful disease conditions, including schizophrenia 285 .…”

Section: Clinical Applicationsmentioning

confidence: 99%

New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

et al. 2023

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Psychiatric genetics has made substantial progress in the last decade, providing new insights into the genetic etiology of psychiatric disorders, and paving the way for precision psychiatry, in which individual genetic profiles may be used to personalize risk assessment and inform clinical decision‐making. Long recognized to be heritable, recent evidence shows that psychiatric disorders are influenced by thousands of genetic variants acting together. Most of these variants are commonly occurring, meaning that every individual has a genetic risk to each psychiatric disorder, from low to high. A series of large‐scale genetic studies have discovered an increasing number of common and rare genetic variants robustly associated with major psychiatric disorders. The most convincing biological interpretation of the genetic findings implicates altered synaptic function in autism spectrum disorder and schizophrenia. However, the mechanistic understanding is still incomplete. In line with their extensive clinical and epidemiological overlap, psychiatric disorders appear to exist on genetic continua and share a large degree of genetic risk with one another. This provides further support to the notion that current psychiatric diagnoses do not represent distinct pathogenic entities, which may inform ongoing attempts to reconceptualize psychiatric nosology. Psychiatric disorders also share genetic influences with a range of behavioral and somatic traits and diseases, including brain structures, cognitive function, immunological phenotypes and cardiovascular disease, suggesting shared genetic etiology of potential clinical importance. Current polygenic risk score tools, which predict individual genetic susceptibility to illness, do not yet provide clinically actionable information. However, their precision is likely to improve in the coming years, and they may eventually become part of clinical practice, stressing the need to educate clinicians and patients about their potential use and misuse. This review discusses key recent insights from psychiatric genetics and their possible clinical applications, and suggests future directions.

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Section: Clinical Applicationsmentioning

confidence: 99%

New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

et al. 2023

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“…In this setting, embryos generated by in vitro fertilization are screened for their genetic predisposition to complex, polygenic diseases and ranked for transfer for pregnancy. This technology is considered by many as unethical ( 28 ; 29 ; 30 ) and is also widely believed to have little ability to identify embryos with substantially lower risk ( 31 ; 32 ). However, several simulation and modeling studies ( 9 ; 10 ; 33 ; 34 ) found that even for diseases with poorly predictive PGS, selection of the lowest-risk embryo could lead to substantial relative risk reduction.…”

Section: Discussionmentioning

confidence: 99%

Predicting the direction of phenotypic difference

Gokhman,

Harris,

Carmi

et al. 2024

Preprint

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Predicting precise phenotypes from genomic data is a key goal in genetics, but it is often hampered by incomplete genotype-to-phenotype data. Here, we describe a more attainable approach than quantitative predictions, aimed at qualitatively predicting phenotypic differences, i.e., which individual has the higher phenotypic value. This approach could be useful in a wide variety of scenarios, e.g., estimating if an individual has an increased disease risk, or if genetically modifying a crop would increase yield. To investigate whether limited genotype-to-phenotype information can still be used to predict which individual has the higher phenotypic value, we developed an estimator of the ratio between known and unknown effects on the phenotype. We formalize a model to delineate the scenarios in which accurate predictions can be achieved and evaluate performance in real-world data from tens of thousands of individuals from either the same family, same population, different populations, or separate species. We find that even in phenotypes where only a small fraction of the genetic effects are known, our estimator can allow for the identification of the individual with the higher phenotypic value, often with over 90% accuracy. We also find that our approach circumvents some of the limitations in transferring association data across populations. Overall, our study introduces an approach for accurately predicting a key feature of phenotypes—their direction—and suggests that more phenotypic information can be extracted from genomes than previously appreciated.

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“…In the near future, the direct‐to‐consumer genetic testing market may begin to offer publicly available genetic tests for “musical ability.” Additionally, these scores could be used for eugenic purposes (e.g., as part of prenatal testing). Some in vitro fertilization clinics already offer polygenic embryo screening (PES 73 ), that is, screening embryos for genetic risk of complex diseases, including psychiatric disorders, based on polygenic risk scores, 74 and might someday incorporate PGS for musicality into their services. There is no demonstrated clinical utility to PES for musical traits or most polygenic traits for that matter; 75 for this reason, we believe it would be inappropriate and unethical to incorporate it into clinical practice.…”

Section: Integrating Ethical and Social Perspectives Into This Nascen...mentioning

confidence: 99%

Confronting ethical and social issues related to the genetics of musicality

Gordon

Martschenko

Nayak

et al. 2023

Annals of the New York Academy of Sciences

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New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh potential risks and benefits of these studies and use of their outcomes. Here we bring together diverse perspectives (complex trait genetics, music cognition, musicology, bioethics, and neuroscience) to guide ethical use of this new knowledge. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication about the research. MAIN TEXTWith the publication of the first large-scale Genome-wide Association Study (GWAS) of a musicality trait, 1 timely ethical and social considerations require discussion. This recent GWAS of beat synchronization reveals the genetic architecture of the fascinating human tendency to move in time with a musical "beat" (or pulse), a behavior ubiquitous in musical cultures. 2,3 Neurobiological and psychological evidence previously highlighted how beat synchronization is integral to music-making, dancing, singing, within the landscape of musicality as a platform for exploring fundamental mechanisms of sensation, prediction, coordination, and reward. Moreover, music plays a profound social function for humans and there is mounting evidence of

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Concerns about the use of polygenic embryo screening for psychiatric and cognitive traits

Cited by 17 publications

References 78 publications

New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

Predicting the direction of phenotypic difference

Confronting ethical and social issues related to the genetics of musicality

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