Validity of polygenic risk scores: are we measuring what we think we are?

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...