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ELSI Virtual Forum

Polygenic Risk Scores & Behavioral Traits: Interrogating the Science & Ethics


The development and aggregation of huge datasets of genomic information, often including hundreds of thousands of participants, has enabled large-scale genome-wide association studies (GWAS) of a variety of phenotypes. Although much of this work has focused on medical conditions, increasing effort is going into analyses of behavioral phenotypes (e.g., same-sex sexual behavior) and social outcomes (e.g., educational attainment, income). These studies evoke a variety of concerns that are the focus of this session. This session will begin with an overview by Dalton Conley of the construction of polygenic risk scores (PRS), then move into discussion of their application to social traits. He will illustrate this with a description of recent work using polygenic scores for educational attainment, including the development of predictive models and their limits. Use of polygenic scores in the social sciences, however, goes beyond predictive models, and Prof. Conley will explain how they can be employed to increase the validity of analyses of the impact of social variables.

Next, Steve Hyman will describe reasons for skepticism about some of the ways in which polygenic scores are being applied and interpreted. He will explain the basis for that skepticism in the science of polygenic risk, including the difficulty of applying scores developed from one population group to other groups not well-represented in the reference set, and the intrinsic relationship between genetic and social influences on outcomes. Prof. Hyman will also describe the ELSI issues that arise from generation of polygenic scores for abnormal behavioral conditions. The session will conclude with time for comments and discussion from the audience.

Lastly, Michelle Meyer will describe the ELSI questions that arise in particular from the application of polygenic scores to behavioral and social outcomes. These include research ethics issues, illustrated by use of data from the U.K. Biobank; questions about distinctions between health-related and non-health-related studies with polygenic scores; and issues regarding consent. Prof. Meyer will present highlights from findings from studies conducted by Geisinger’s biobank and the Estonian biobank on public views about the legitimacy of using biobank data for development of polygenic scores on a variety of behavioral and social outcomes.

Speakers: Dalton Conley, PhD; Steve Hyman, MD; Michelle Meyer, JD, PhD

Moderator: Paul Appelbaum, MD

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