Imaging may play a role in finding out how these genes create risk for illness through their impact on the brain, by comparing brain scans of carriers versus non-carriers. One such example is the ZNF804A story. A variant within ZNF804A was the first genome-wide significant SNP associated with risk for schizophrenia (O’Donovan et al. 2008). The function of this variant was initially not clear. Prominent papers later appeared (e.g., Esslinger et al. 2009) using imaging to establish disturbed connectivity as a neurogenetic risk mechanism for psychosis. They showed that some variant in ZNF804A (or some variations in linkage disequilibrium with them) must be functional in the human brain. This was one of many early studies to validate the intermediate phenotype strategy in psychiatry.
