Chunk #25 — Polygenic Risk Scores: A Bridge Between Population Variation and Individual Differences — PRS Practicalities — Technical Considerations. — Improvements in PRS estimation:
Method improvement for PRS estimation is an active area of research, with several new approaches only recently proposed - here, we briefly highlight two. One approach, LDpred (Vilhjalmsson et al., 2015), takes into account the LD between markers, thus eliminating the need for LD-thinning, which may limit the variance explained by PRS in some cases. LDpred estimates posterior mean effect sizes based on LD patterns from a reference genome, by specifying an LD radius (i.e., number of SNPs that are accounted for on either side of another SNP), and has been found to have better accuracy and calibration. For example, in the same target sample, LDpred explains 25% of the variance in schizophrenia compared to 18% from traditional PRS. Another approach, MTAG (Multi-Trait Analysis of GWAS; (Turley et al., 2017)), which may be thought of as an extension of traditional meta-analysis, enables the joint analysis of several traits, resulting in improved PRS precision. MTAG takes advantage of the increasing number of publicly-available GWAS summary statistics, and the development of techniques which can estimate trait heritability and genetic correlations from summary
