Evaluating HWE and Association in Genome-Wide Association Studies: A Unified Procedure

The document presents a new method for evaluating SNPs in genome-wide association studies (GWASs) that integrates the Hardy-Weinberg equilibrium (HWE) test with the association test, using a conditional genotype-based approach. This method, which conditions the Pearson $χ^2$-statistic on the HWE $χ^2$-statistic in the control group, is shown through simulations to be more powerful than existing methods. It improves SNP ranking by incorporating HWE into p-value calculations, demonstrated in an alopecia study. The proposed test eliminates the need for separate HWE testing, enhances power and interpretability, and makes replication more cost-effective, benefiting subsequent fine mapping efforts.