The genetic architecture of a trait is determined by the number of causal genetic variants, and their corresponding effect sizes. Assuming constant heritability, more causal genetic variants reduce the average effect size. Most complex traits are highly polygenic, meaning that many causal SNPs have small effect sizes that are not yet genome-wide significant (i.e., p < 5e-8). Because smaller effects are more difficult to accurately estimate, highly polygenic traits are more difficult to predict (24; 25). As discovery sample sizes increase, the estimation error for each SNP effect shrinks, improving predictive power (26).
