Genetic model selection for a case–control study and a meta-analysis

A case-control study often compares the prevalence of a specific disease among persons with normal alleles and persons with variant alleles, which generates an odds ratio (OR). The most common type of allele variation, single-nucleotide polymorphism, consists of a major allele (M) and a minor allele (m). Thus, the genotype can be a major allele homozygote (MM), a heterozygote (Mm) or a minor allele homozygote (mm). Odds are given for each genotype, and a pair of odds generates an OR. Summarizing data using two-by-two contingency is the simplest method of estimating an OR. Thus, dominant, multiplicative, recessive, and over-dominant models are often used. Traditionally, researchers used to calculate ORs using many models and then select the best model from among these calculated ORs. This may cause problems due to multiple comparisons. Therefore, we should choose the best model before calculating the OR for each model. In this article, we will discuss how to choose the best model among many subject-level models when evaluating the impact of the MM/Mm/mm genotype on the disease prevalence.