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IB Seminar - Dr. Arbel Harpak, Columbia University
Tuesday, March 10, 2020, 11:00am - 12:00pm
Contact ibfrontdesk@austin.utexas.edu

TITLE: "Interpreting and Deconstructing Polygenic Scores"


Location: MBB 1.210
Interpreting and deconstructing polygenic scores
Dr. Arbel Harpak
Simons Society Fellow, Columbia University

A polygenic score is a predictor of a person’s trait value computed from his or her genotype. Polygenic scores sum over the genetic effects of the alleles carried by a person—as estimated in a genome-wide association study (GWAS) for the trait of interest. Fields as diverse as clinical risk classification, evolutionary genetics, social sciences and embryo selection are rapidly adopting polygenic scores.

I will show that the prediction accuracy of polygenic scores can be highly sensitive to tiny biases in GWAS effect estimates, and further that the prediction accuracy of polygenic scores depends on characteristics such as the socio-economic status, age or sex of the people in which the GWAS and the prediction are conducted. These dependencies highlight the complexities of interpreting polygenic scores and the potential for serious inequities in their application in the clinic and beyond.

A key reason for these dependencies is in the fact that GWAS estimates are also influenced by factors other than direct genetic effects—including population structure confounding, mating patterns, indirect genetic effects of relatives and other gene-by-environment interactions. I will discuss the development of tools to tease apart the different factors contributing to GWAS associations, and ultimately improve the prediction ability and our interpretation of polygenic scores.

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