Genetic data and Global populations: Do we have enough data to do a genetic study on the correlation between mental illness and drug use in a South African population?

by Mellie Msipa

Studies into Crystal Meth and its association with Schizophrenia

We all know that drug abuse is “bad”. Cocaine, Benzodiazepines and Methamphetamine (Crystal Meth) are just some of the drugs that people abuse, and if you were like me and grew up around people that weren’t always politically correct, then you probably heard the saying that ‘drugs kill your brain cells, and make you mentally ill’. Although phrases like this are often thrown at children and adolescence as a scare tactic to deter them from experimenting with opioids, some researchers in South Africa, Germany and the United States may have taken it quite literally, when they investigated and later published their paper on, “Schizophrenia Polygenic Risk and Brain Structural Changes in Methamphetamine-Associated Psychosis in a South African Population” (Passchier, et al., 2020).

How was the investigation conducted?

Saliva samples were collected for various cases and controls. The cases included patients that had Methamphetamine-associated psychosis (MAP) and patients who had a methamphetamine dependence (MD) and no psychosis. Healthy controls (HC) were also investigated for comparative purposes (Passchier, et al., 2020). The samples were genotyped, and quality control was performed on the data. Principal component analysis was performed to account for stratification, Structural brain imaging was performed to investigate the brain regions that have been linked to MAP and schizophrenia (Passchier, et al., 2020). Polygenic risk scoring was performed to determine the effect of the risk variants on the phenotype/ disease. Statistical analysis was then performed using tests, one of which included a t-test that tested the differences between the two case groups and the healthy group.

The results found the following:

The aim of the study was to determine how the polygenic risk scoring data from a European ethnicity based GWAS study on MAP compared with the brain measurement volumes tested in the South African MAP patients (Passchier, et al., 2020). The results of the investigation showed no significant association between Schizophrenia-derived risk scoring and the MAP disease diagnosis in patients.

The researchers also found that there was no correlation between the polygenic risk scoring and the volume measures from the different parts of the brain in the patients. The paper explains that that the negative result could be since Schizophrenia polygenic risk scores have no relation to the brain volume measurements seen in the case samples (Passchier, et al., 2020).

Due to the lack of GWAS data available for patients of African descent, the researchers found that people of African descent had the lowest polygenic score performance, and they concluded that the Polygenic risk score data from European population based studies were not applicable for the South African patients studied in this paper (Passchier, et al., 2020).

Ultimately the results for the study were inconclusive due to the limitations due to sample size, stratification bias and the risk of misclassification from the diagnostic interviews.

Impact of this research:

African health care systems like South Africa saw that mental and substance used disorders like schizophrenia increased by over 50% in the different populations just between the years 2000 and 2015 (Sankoh, et al., 2018). Diseases like Schizophrenia have led to over 14% of deaths globally and previous studies have found 145 genome wide significant loci for Schizophrenia ( Stevenson, et al., 2019). Mental health is a global problem, however very little genetic data is available/ recorded for mental health diseases that plague non-white populations. While the results of the study could not show any strong correlation between Schizophrenia and Crystal Meth use, the design of the study highlighted the need for more studies into non-European populations, like African populations that could uncover new risk variants.

References:

Stevenson, A. et al., 2019. Populations-Psychosis (NeuroGAP- Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda. BMJ, Volume 9, pp. 1- 9.

Passchier, R. V. et al., 2020. Schizophrenia Polygenic Risk and Brain Structural Changes in Methamphetamine-Associated Psychosis in South African Population. Fronteirs in Genetics, Volume 11, pp. 1- 7.

Sankoh, O., Sevalie, S. & Weston, M., 2018. Mental health in Africa. The Lancet Global Health, Volume 6, pp. 954- 955.

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