Clearly, these studies aggregate data from cohorts that are heterogeneous in terms of duration of illness, disease etiology, medication history, demographics, exposure to potentially neuroprotective substances such as lithium, and many other factors. But part of the richness of the ENIGMA efforts is that they afford sufficient power to begin to see which of these factors—including geographic factors, perhaps—affect disease expression in the brain and the universality, or otherwise, of the biomarkers of brain disease. Based on these findings, a key direction for ENIGMA is to see how genes that affect the brain relate to genes that affect risk for psychiatric illness (identified by the Psychiatric Genomics Consortium, https://pgc.unc.edu/), to identify shared biology between brain characteristics and disease. A collaboration between ENIGMA and the PGC is now underway to study these relationships.
