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Updated: Jun 29, 2025

Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization
Published on: July 27, 2021
The effects of case/control ratio and sample size on genome-wide association studies: A simulation study
Ali Osman Turgut1, Davut Koca2
1Faculty of Veterinary Medicine, Department of Animal Science, Siirt University, Siirt, Turkey.
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.
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