A review: simulation tools for genome-wide interaction studies.

Genome-wide association study (GWAS) is essential for investigating the genetic basis of complex diseases; nevertheless, it usually ignores the interaction of multiple single nucleotide polymorphisms (SNPs). Genome-wide interaction studies provide crucial means for exploring complex genetic interactions that GWAS may miss. Although many interaction methods have been proposed, challenges still persist, including the lack of epistasis models and the inconsistency of benchmark datasets. SNP data simulation is a pivotal intermediary between interaction methods and real applications. Therefore, it is important to obtain epistasis models and benchmark datasets by simulation tools, which is helpful for further improving interaction methods. At present, many simulation tools have been widely employed in the field of population genetics. According to their basic principles, these existing tools can be divided into four categories: coalescent simulation, forward-time simulation, resampling simulation, and other simulation frameworks. In this paper, their basic principles and representative simulation tools are compared and analyzed in detail. Additionally, this paper provides a discussion and summary of the advantages and disadvantages of these frameworks and tools, offering technical insights for the design of new methods, and serving as valuable reference tools for researchers to comprehensively understand GWAS and genome-wide interaction studies.