Genome-wide association studies (GWAS), combined with large sample sizes reflective of collaboration across many individual studies, have since been used to perform a hypothesis free search of the genome (Figure 1a). GWAS largely focuses on common (i.e., frequency > 1%) DNA variants, known as single-nucleotide polymorphisms (SNPs) that generally consist of two alleles, and some more rare copy number variants (CNVs). The output of a GWAS is referred to as a set of summary statistics, which consist of regression relationships between each SNP and the trait of interest. In the context of psychiatric GWAS studies that typically employ samples of cases and controls, the GWAS then tests for differences in allele frequencies across individuals with and without a particular disorder. These efforts have expanded rapidly in the last decade, with the latest efforts for major depressive disorder (MDD) and schizophrenia (SCZ) identifying over 102 and 270 associated variants, respectively (Howard et al., 2019; Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2020).
