Interpreting population- and family-based genome-wide association studies in the presence of confounding
GWASs aim to estimate direct effects of genotype on an individual’s phenotype, but this can be subject to genetic and environmental confounds and “indirect” genetic effects of relatives’ genotypes. This study presents a theoretical analysis of the influence of confounders in population-based and within-family GWASs, showing that, while family-based studies are more rigorous, they still carry subtle issues that arise from confounding.