The effects of case/control ratio and sample size on genome‐wide association studies: A simulation study

Abstract Background Genome‐wide association studies (GWAS) is a useful tool for the detection of disease or quantitative trait‐related genetic variations in the veterinary field. For a binary trait, a case/control experiment is designed in GWAS. However, there is limited information on the optimal case/control and sample size in GWAS. Objectives In this study, it was aimed to detect the effects of case/control ratio and sample size for GWAS using computer simulation under certain assumptions. Method Using the PLINK software, we simulated three different disease scenarios. In scenario 1, we simulated 10 different case/control ratios with increasing ratio of cases to controls. In scenario 2, we did versa of scenario 1 with the increasing ratio of controls to cases. In scenarios 1 and 2, sample size gradually was increased with the change case/control ratios. In scenario 3, the total sample size was fixed to 2000 to see real effects of case/control ratio on the number of disease‐related single nucleotide polymorphisms (SNPs). Results The results showed that the number of disease‐related SNPs were the highest when the case/control ratio is close to 1:1 in scenarios 1 and 2 and did not change with an increase in sample size. Similarly, the number of disease‐related SNPs was the highest in case/control ratios 1:1 in scenario 3. However, unbalanced case/control ratio caused the detection of lower number of disease‐related SNPs in scenario 3. The estimated average power of SNPs was highest when case/control ratio is 1:1 in all scenarios. Conclusions All findings led to the conclusion that an increase in sample size may enhance the statistical power of GWAS when the number of cases is small. In addition, case/control ratio 1:1 may be the optimal ratio for GWAS. These findings may be valuable not only for veterinary field but also for human clinical experiments.