Interpreting population- and family-based genome-wide association studies in the presence of confounding
Fig 3
The impact of assortative mating on the average squared effect-size estimate in population and within-family GWASs.
Same-trait assortative mating of strength ρ = 0.2 occurs among parents in generations 0–20; mating is random before and after this period. Under random mating, the average squared effect-size estimates exceed the true average squared effect size (yellow line) because random drift generates chance local LD with causal alleles that inflates the variance of effect-size estimation (e.g., [18]). The magnitude of this variance inflation depends on the GWAS design and sample size, and the effect of assortative mating and its cessation should be judged in reference to it. To guide the eye in this judgment, the faint horizontal lines in (A) and (B) show the average squared effect-size estimate in the last 20 generations of the initial burn-in period of random mating. The inset in (B) zooms in on the sibling GWAS profile, omitting the population GWAS profile for clarity. Profiles are averages across 5,000 replicate simulation trials. Simulation details can be found in the Methods and the code can be found at https://doi.org/10.5281/zenodo.10520811.