Biostatistics Weekly Seminar

Polygenic Risk Scores: What Are We Measuring?

Cecile Janssens, PhD
Emory University

Polygenic risk scores (PRSs) have become the standard for quantifying genetic liability in the prediction of disease risks. PRSs are generally constructed as weighted sum scores of risk alleles using effect sizes from genome-wide association studies as their weights. The construction of PRSs is being improved with more appropriate selection of independent single-nucleotide polymorphisms (SNPs) and optimized estimation of their weights but is rarely reflected upon from a theoretical perspective, focusing on the validity of the risk score. Borrowing from psychometrics, I will discuss the validity of PRSs and introduces the three main types of validity that are considered in the evaluation of tests and measurements: construct, content, and criterion validity. I will then discuss several topics that challenge the validity of PRS, among which are their claimed independence of clinical risk factors, the consequences of relaxing SNP inclusion thresholds and the selection of SNP weights. Is the weighted sum score valid enough? Or can we think of alternative modeling strategies that might better reflect the underlying biological pathways?

Zoom (Link to Follow)
26 August 2020

Speaker Itinerary

Topic revision: r1 - 21 Aug 2020, AndrewSpieker

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