The unquestionable success of GWAS in identifying strong and replicable associations for so many human diseases is intriguing given that the additive logistic regression model generally used is rudimentary. The dependent variable is disease status (1 = yes, 0 = no), the continuous independent variable is a SNP genotype (coded as the number of copies of the minor allele or as the imputed allelic dosage, 0–2), plus covariates like principal components to adjust for ancestry. It is possible that MDD is distinctive, and that the additive logistic model is not an adequate approximation of the genetic architecture of MDD (see Kohli et al.26). There are numerous alternative genetic architectures, although many are at least partly detectable using an additive model.
