Polygenic scoring accuracy varies across the genetic ancestry continuum

Abstract Polygenic scores (PGSs) have limited portability across different groupings of individuals (for example, by genetic ancestries and/or social determinants of health), preventing their equitable use 1–3 . PGS portability has typically been assessed using a single aggregate population-level statistic (for example, R 2 ) 4 , ignoring inter-individual variation within the population. Here, using a large and diverse Los Angeles biobank 5 (ATLAS, n = 36,778) along with the UK Biobank 6 (UKBB, n = 487,409), we show that PGS accuracy decreases individual-to-individual along the continuum of genetic ancestries 7 in all considered populations, even within traditionally labelled ‘homogeneous’ genetic ancestries.…

• UH
  UCLA Health System
• NI
  National Institutes of Health

  Awards: R01HG009120, R01MH115676, UL1TR001881, U01HG011715
• DG
  David Geffen School of Medicine, University of California, Los Angeles

  Award: UL1TR001881
• CA
  Clinical and Translational Science Institute, University of California, Los Angeles

  Award: UL1TR001881