Interpreting population- and family-based genome-wide association studies in the presence of confounding.

ABSTRACT: A central aim of genome-wide association studies (GWASs) is to estimate direct genetic effects: the causal effects on an individual's phenotype of the alleles that they carry. However, estimates of direct effects can be subject to genetic and environmental confounding and can also absorb the "indirect" genetic effects of relatives' genotypes. Recently, an important development in controlling for these confounds has been the use of within-family GWASs, which, because of the randomness of mendelian segregation within pedigrees, are often interpreted as producing unbiased estimates of direct effects. Here, we present a general theoretical analysis of the influence of confounding in standard population-based and within-family GWASs. We show that, contrary to common interpretation, family-based

SUBMITTER: Veller C 

PROVIDER: S-EPMC11008796 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature