Chunk #32 — Polygenic Risk Scores: A Bridge Between Population Variation and Individual Differences — PRS Practicalities — Technical Considerations. — Differences from other heritability metrics:
Even though they represent the additive effects of segregating loci, PRS are distinct from twin-heritability and SNP-heritability. SCZ-PRS explain ~18% of the variance in the disorder in independent samples (Schizophrenia Working Group of the Psychiatric Genomics, 2014); family/twin-h2 and SNP-h2 are 80% and 41% respectively (Sullivan et al., 2017). Estimates of twin-h2 are based on latent sources of additive (and in some cases, non-additive) genetic factors and assume uniform effects of all segregating loci. Furthermore, they rely on certain assumptions, some of which can be reasonably questioned (e.g., random mating). PRS represent a portion of this genetic variance that is attributable to a set of uncorrelated loci, and are less assumption-laden. In fact, PRS approaches have been used to demonstrate the widespread occurrence of assortative, (non-random) mating - for instance, polygenic liability to educational attainment in one spouse accounts for 14–19% of the partner’s education outcomes (Hugh-Jones, Verweij et al. 2016). SNP-h2, calculated with a variety of methods [Genetic Complex Traits Analysis: GCTA (Yang et al., 2011); Linkage Disequilibrium Score Regression: LDScR; (Bulik-Sullivan et al., 2015)], may be used to
