Schizophrenia Polygenic Risk and Brain Structural Changes in Methamphetamine-Associated Psychosis in a South African Population

Background: The genetic architecture of psychotic disorders is complex, with hundreds of genetic risk loci contributing to a polygenic model of disease. Overlap in the genetics of psychotic disorders and brain measures has been found in European populations, but has not been explored in populations of African ancestry. The aim of this study was to determine whether a relationship exists between a schizophrenia-derived PRS and (i) methamphetamine associated psychosis (MAP), and (ii) brain structural measures, in a South African population.

Methods: The study sample consisted of three participant groups: 31 individuals with MAP, 48 with apsychotic methamphetamine dependence, and 49 healthy controls. Using PRSice, PRS was generated for each of the participants with GWAS summary statistics from the Psychiatric Genomics Consortium Schizophrenia working group (PGC-SCZ2) as the discovery dataset. Regression analyses were performed to determine associations of PRS, with diagnosis, whole brain, and regional gray and white matter measures.

Results: Schizophrenia-derived PRS did not significantly predict MAP diagnosis. After correction for multiple testing, no significant associations were found between PRS and brain measures across all groups.

Discussion: The lack of significant associations here may indicate that the study is underpowered, that brain volumes in MAP are due to factors other than polygenic risk for schizophrenia, or that PRS derived from a largely European discovery set has limited utility in individuals of African ancestry. Larger studies, that include diverse populations, and more nuanced brain measures, may help elucidate the relationship between schizophrenia-PRS, brain structural changes, and psychosis.

Conclusion: This research presents the first PRS study to investigate shared genetic effects across psychotic disorders and brain structural measures in an African population. Ancestrally comparable discovery datasets may be useful for future African genetic research.