Negative selection on complex traits limits phenotype prediction accuracy between populations.

ABSTRACT: Phenotype prediction is a key goal for medical genetics. Unfortunately, most genome-wide association studies are done in European populations, which reduces the accuracy of predictions via polygenic scores in non-European populations. Here, we use population genetic models to show that human demographic history and negative selection on complex traits can result in population-specific genetic architectures. For traits where alleles with the largest effect on the trait are under the strongest negative selection, approximately half of the heritability can be accounted for by variants in Europe that are absent from Africa, leading to poor performance in phenotype prediction across these populations. Further, under such a model, individuals in the tails of the genetic risk distribution may not

SUBMITTER: Durvasula A 

PROVIDER: S-EPMC8059340 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature