Fourth, the discovery of a GWAS hit—in ENIGMA or any other GWAS study—is the beginning of a long road of discovery, especially if the finding is intergenic or in a gene of unknown function. Some genomic screens of anatomical or structural connectivity data have implicated genes such as SPON1 (Jahanshad et al. 2013b) and FRMD6 (Ryles et al. 2012) that were discovered in later case–control studies to be risk genes for AD (Hong et al. 2012; Sherva et al. 2013). Functional validation of genetic variants reliably implicated in large scale studies will be the way we learn new biological processes and further our understanding of risk for psychiatric diseases.
