To do this, they used genetic information gathered from the blood of 4,196 cases and 3,827 controls from the Molecular Genetics of Schizophrenia study. Among these participants, they identified patterns of genetic polymorphisms (SNPs) that cluster within individuals (without regard for whether they have Schizophrenia or not). This resulted in 723 clusters. Then, they calculated the “risk” for having Schizophrenia from each of these clusters, and identified 42 genetic polymorphism clusters that were associated with a 70% or greater increase in risk for having Schizophrenia. They then re-tested the association between these genetic polymorphism clusters and risk for Schizophrenia in two other studies of Schizophrenia with more than 1000 more people.
The research team then identified distinct clinical features (phenotypes) of the individuals in the MGS study that account for different presenting symptoms of Schizophrenia (primarily positive symptoms versus primarily negative symptoms), different trajectories of the illness (people who became very ill very quickly, versus those whose onset was more slowly progressing). Once they identified clinical features that were distinct, they calculated the association between each of their genetic polymorphism clusters and these clinical features. They found that some genetic clusters were associated with their clinical features. Again, they re-tested their findings in two additional large samples.
The result of this highly complex and tedious work was 8 genotype-phenotype relationships and concluded that what we call Schizophrenia today may actually be several distinct clinical syndromes with different genotypic networks. By identifying these genetic polymorphism clusters, the research team was able to account for 90% of the clinical cases, which is much improved from the 25% accounted for by past approaches. Unfortunately, this creates a problem for anyone who studies Schizophrenia, given that it is already challenging to study a phenomenon that occurs in 1% of the population, but now those subgroups are likely even smaller. Alas, we would not be scientists if we didn’t want to conquer the seemingly impossible.
Furthermore, I would be remiss as a clinical psychologist if I didn’t mention that this article also speaks to common stereotypes about mental illness. Schizophrenia has many faces and usually won’t look like Russell Crowe in A Beautiful Mind. This goes for many different forms of mental illness. Don’t dismiss a person’s suffering because it doesn’t always look the same. The best, and most far-reaching example I can give of this, is the mood difficulties common to depression. Sometimes depression can look like sadness and isolation, other times it can look more like irritability and anger, but both cases indicate equal human suffering. The homeless person outside your neighborhood park may be unusual, but they are still a human being who seeks to be understood.
Arnedo, J., Svrakic, D. M., del Val, C., Romero-Zaliz, R., Hernández-Cuervo, H., Fanous, A. H., ... & Molecular Genetics of Schizophrenia Consortium. (2014). Uncovering the hidden risk architecture of the schizophrenias: Confirmation in three independent genome-wide association studies.