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Genetics of schizophrenia in the South African Xhosa.

ABSTRACT: Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide.

SUBMITTER: Gulsuner S

PROVIDER: S-EPMC9558321 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Genetics of schizophrenia in the South African Xhosa.

Gulsuner S S Stein D J DJ Susser E S ES Sibeko G G Pretorius A A Walsh T T Majara L L Mndini M M MM Mqulwana S G SG Ntola O A OA Casadei S S Ngqengelele L L LL Korchina V V van der Merwe C C Malan M M Fader K M KM Feng M M Willoughby E E Muzny D D Baldinger A A Andrews H F HF Gur R C RC Gibbs R A RA Zingela Z Z Nagdee M M Ramesar R S RS King M-C MC McClellan J M JM

Science (New York, N.Y.) 20200101 6477

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical ...[more]

PMID: 32001654

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Project description:IntroductionAdvances in genomics research have raised several ethical concerns. One concern is the potential impact of genomics research on stigma experienced by people affected by a disease. Studies have found that the type of illness as well as disease causal beliefs impact on the relation between genetic attribution and stigma. This study explored the potential impact of genetic attribution of disease on stigma among Xhosa people with Rheumatic Heart Disease (RHD).MethodsStudy participants were 46 Xhosa people with RHD living in the Western Cape Province of South Africa. Using video vignettes in 7 focus group discussions we explored whether and how genetic attribution may impact on disease-stigma. Vignettes introduced participants to non-genetic and genetic causal explanations and were followed-up with a series of open-ended questions eliciting their perceptions of non-genetic disease causes as well as genetic causation and its impact on internalised stigma.ResultsThis study found that Xhosa people with RHD have a general understanding of genetics and genetic attribution for disease. Additionally, and not withstanding their genetic knowledge, these participants hold multiple disease causal beliefs including genetic, infectious disease, psychosocial, behavioural and cultural explanations. While there was evidence of internalised stigma experiences among participants, these appeared not to be related to a genetic attribution to the disease.DiscussionThe findings of this study provide clues as to why it is unlikely that a genetic conceptualisation of disease impacts internalised stigma experiences of Xhosa people. The causal explanations provided by participants reflect their cultural understandings and their context, namely, living in low-income and poverty-stricken environments. Divergence in these findings from much of the evidence from high-income countries emphasises that context matters when considering the impact of genetic attribution on stigma and caution against generalising findings from one part of the globe to another.

Project description:ObjectiveLarge-scale studies have revolutionized biomedical research, and neurocognitive tests can help elucidate the biological basis of neuropsychiatric diseases. However, studies have predominantly been conducted in Western settings. We describe the development and validation of a computerized battery (PennCNB) with the Xhosa population of South Africa.MethodIndividuals with schizophrenia (n = 525) and a normative comparison group (n = 744) were balanced on age, sex, education, and region. Participants provided blood samples, were assessed psychiatrically, and were administered a PennCNB translation to isiXhosa, including measures of executive functions, episodic memory, complex cognition, social cognition, and sensorimotor speed. Feasibility was examined with test completion rates and input from administrators, and psychometric structural validity and associations with clinical and demographic characteristics were examined.ResultsTests were well tolerated by participants, as >87% had one (or fewer) test missing. Results suggested a similar factor structure to prior PennCNB studies in Western contexts, and expected age and sex effects were apparent. Furthermore, a similar profile of schizophrenia was observed, with neurocognitive deficits most pronounced for executive functions, especially attention, as well as memory, social cognition, and motor speed relative to complex cognition and sensorimotor speed.ConclusionsResults support the feasibility of implementing a culturally adapted computerized neurocognitive battery in sub-Saharan African settings and provide evidence supporting the concurrent validity of the translated instrument. Thus, the PennCNB is implementable on a large scale in non-Western contexts, shows expected factor structure, and can detect cognitive deficits associated with neuropsychiatric disorders. Obtaining valid measures of cognition by nonspecialized proctors is especially suitable in resource-limited settings, where traditional testing is prohibitive. Future work should establish normative standards, test-retest reliability, and sensitivity to treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dataset Information

Genetics of schizophrenia in the South African Xhosa.

Publications

Genetics of schizophrenia in the South African Xhosa.

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