Description
Laura Schultz, PhD, will discuss the surprising lack of consistency between polygenic scores (PGS) computed from subsequent generations of consortia-produced discovery GWAS for height, post-traumatic stress disorder, and type-2 diabetes. For a given trait, PGS are only modestly correlated at the level of the individual subject, and different individuals are identified at the upper quantiles of the PGS distributions.
Overview of Presentation
- PGS calculated from pairs of same-ancestry discovery GWAS show only modest correlation with each other despite there being near-perfect genetic correlation between the discovery GWAS.
- A series of height GWAS in the UK Biobank suggests that correlation between PGS is strongly dependent on the extent of sample overlap between the discovery GWAS.
- Focusing on the upper tail of the PGS distribution, different discovery GWAS do not consistently identify the same individuals. The degree of overlap decreases sharply as higher quantiles, less heritable traits, and different-ancestry GWAS are considered.
- PGS computed from different discovery GWAS have only modest correlation at the individual level, underscoring the need to proceed cautiously with integrating PGS into precision medicine applications.
