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Principal Investigator: SHAI CARMI
Organization: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
Fiscal Year: 2024
Award: $680,434
Funding agency: National Human Genome Research Institute
PROJECT SUMMARY
Preimplantation genetic testing (PGT) has been utilized for years to avoid implantation of embryos
harboring rare monogenic disease-causing alleles or aneuploidies. However, recent progress in complex trait
genetics, coupled with the technical ability to generate accurate genome-wide genotypes from single-cell input,
has made it possible to genetically screen embryos for common polygenic traits and disease risk. While
popular media has raised the specter of ‘‘designer babies,’’ and private industry has begun to offer services of
dubious merit, little empirical work has been done to quantify the utility of polygenic embryo screening (PES),
examine its ethical implications, and assess stakeholders’ perspectives. Unlike conventional PGT, polygenic
risk scores are intrinsically probabilistic and multifaceted. The inherent ambiguities of PES requires careful
consideration in order for clinicians, policymakers, and the general public to make informed decisions about the
potential consequences of implementing polygenic embryo screening. Moreover, although research
momentum for polygenic risk scores has grown exponentially in the last few years, there is almost no
independent, empirical data on either: 1) the potential ability of PES to produce desired outcomes under
various real-world scenarios; or 2) the perspectives and attitudes of front-line clinicians in the potential clinical
application of polygenic risk scores, especially in the prenatal context.
In order to build an initial framework for the consideration of the ethical, legal, and social implications
(ELSI) of PES, it is necessary to establish two sets of empirical parameters: first, the statistical properties that
will shape the potential application of polygenic risk scores in the prenatal setting; and second, the attitudes
and perspectives of clinicians who would be at the front lines of administering PES, including genetic
counselors, reproductive endocrinologists, and obstetricians. The proposed study therefore aims to quantify
the range of realistic outcomes of PES in the context of disease risk reduction under varying conditions, using
a combination of simulated and real data. We also aim to understand the perspectives of clinicians who would
potentially deliver PES, using both in-depth interviews and a large-scale survey of reproductive clinicians and
geneticists. In the proposed research project, these two aims will be interdigitated and mutually informative;
statistical investigation will be guided by concerns and questions posed by stakeholders, and stakeholder
interviews and surveys will be shaped by the statistical and methodological understanding obtained from our
analyses. On the basis of our results, we will perform ethical analysis of this rapidly evolving technology.
Terms: <Alleles><Allelomorphs><Aneuploid><Aneuploidy><Assisted Reproduction Technology><Assisted Reproductive Technology><Attitude><Blastocyst Implantation><Cancers><Cardiac Diseases><Cardiac Disorders><Cell Body><Cells><Complex Genetic Trait><Confidence Intervals><Coupled><Data><Data Set><Decision Making><Diabetes Mellitus><Disease><Disorder><ELSI><Embryo><Embryo Implantation><Embryonic><Endocrinologist><Ethical Analyses><Ethical Analysis><Ethics><Future><General Population><General Public><Genotype><Heart Diseases><Height><Individual><Industry><Intelligence><Interview><Investigation><Knowledge><Malignant Neoplasms><Malignant Tumor><Mendelian disease><Mendelian disorder><Mendelian genetic disorder><Mental disorders><Mental health disorders><Methodology><Modeling><Motivation><Nidation><Noise><Outcome><Ovum Implantation><Partner in relationship><Patients><Phase><Policy Maker><Polygenic Characters><Polygenic Inheritances><Polygenic Traits><Pre-implantation genetic diagnosis><Pre-implantation genetic testing><Preimplantation Diagnosis><Preimplantation Genetic Diagnosis><Preimplantation genetic testing><Preimplantation testing><Prevalence><Privatization><Property><Psychiatric Disease><Psychiatric Disorder><Publishing><R-Series Research Projects><R01 Mechanism><R01 Program><Reporting><Reproductive Medicine><Research><Research Grants><Research Project Grants><Research Projects><Risk><Risk Reduction><Screening procedure><Services><Shapes><Stigmatization><Survey Instrument><Surveys><Technology><Time><Uncertainty><Work><assistive reproductive technology><clinical applicability><clinical application><design><designing><diabetes><disease risk><disorder risk><doubt><embryo attachment><ethical><ethical legal and social><ethical, legal, and social implication><evidence base><genetic counselor><genome scale><genome-wide><genomewide><heart disorder><interest><malignancy><mate><mental illness><monogenic disease><monogenic disorder><natural Blastocyst Implantation><neoplasm/cancer><pleiotropic effect><pleiotropism><pleiotropy><polygenic risk score><preference><prenatal><psychiatric illness><psychological disorder><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><reproductive><risk-reducing><screening><screening tools><screenings><simulation><single-gene disease><single-gene disorder><stakeholder insights><stakeholder perspectives><theories><trait><unborn><willingness>