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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Dong, Rui Wang, Gao T. DeWan, Andrew T. Leal, Suzanne M. |
| Abstract | The case-only design is a powerful approach to identify gene $\times$ gene and gene $\times$ environment interactions for complex traits. It has been demonstrated that for the case-only design to be valid the genetic and environmental factors must be independent in the population. Additionally, there is a rare disease assumption for the case-only design, but the impact of disease prevalence and other factors, e.g., size of main effects, on type I and II error rates has not been investigated. Through theoretical and extensive simulation studies, we investigated type I error, power, and bias of interaction term for a wide variety of disease prevalences, main and interaction effect sizes, sample sizes, and variant and environmental exposure frequencies. For diseases with prevalence $<$ 4%, the case-only design usually has well controlled type I error rates and is substantially more powerful to detect interactions than the case–control design, but for higher disease prevalences both type I and II error rates can be inflated and the estimate of interaction term biased. However, when one or both main effects are large there can be inflated type I error rate even for low disease prevalences, e.g., $<$ 1%, but if there is no or only one main effect, type I error rate is controlled regardless of the disease prevalence. Additionally, type I error rate can increase with sample size. We determined the upper bound of the disease prevalence in order not to violate the rare disease assumption for the case-only design. To verify that a case-only design study does not have increased type I error rate, the bias of the interaction term should be estimated. Although the case-only design is a powerful method to detect interactions, prevalences for some complex traits are too high to implement this method without increasing type I error rates. |
| Related Links | https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-025-11318-1.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14712164 |
| DOI | 10.1186/s12864-025-11318-1 |
| Journal | BMC Genomics |
| Issue Number | 1 |
| Volume Number | 26 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-03-06 |
| Access Restriction | Open |
| Subject Keyword | Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Gene gene and gene environment interactions Case-only design Complex traits Rare disease |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biotechnology Genetics |
| Journal Impact Factor | 3.5/2023 |
| 5-Year Journal Impact Factor | 4.1/2023 |
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