The first genetic analysis of schizophrenia in an ancestral African population, the South African Xhosa, appears in the journal Science. The study was carried out in the Xhosa population because Africa is the birthplace of all humans, yet ancestral African populations have rarely been the focus of genetics research (There is no evidence that the Xhosa have an unusually high risk of schizophrenia).
The researchers analyzed blood samples collected from 909 individuals diagnosed with schizophrenia and 917 controls living in South Africa. Their study revealed that participants with schizophrenia are significantly more likely to carry rare, damaging genetic mutations compared to participants without schizophrenia.
These rare mutations were also more likely to affect brain and synaptic function. Synapses coordinate the communication between brain nerve cells called neurons; the organization and firing of neuronal synapses are ultimately responsible for learning, memory, and brain function.
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.
The genes and pathways identified by this research inform the understanding of schizophrenia for all human populations, the researchers say. Further studies in African populations might also suggest potential mechanisms for the design of more effective treatments.
"The presence of only a few DNA variations damaging to synaptic function could have an outsized effect on schizophrenia," says co-author. "While these variants differ from person to person, we believe they may disrupt neural pathways that elevate risk for schizophrenia."
The relative lack of genetics studies in Africa leaves a major gap in understanding human genetics. Almost 99 percent of human evolution took place in Africa after the first modern humans originated and before humans migrated from Africa to Europe and Asia 50,000 to 100,000 years ago. Because of the lack of studies in Africa, many generations of human genetic history are missing from our understanding of human adaptation and of human disease. Studies of ancestral African populations like the Xhosa have more diverse background DNA, which facilitates the identification of truly rare mutations.
https://www.mailman.columbia.edu/public-health-now/news/new-clues-genetic-origins-schizophrenia
https://science.sciencemag.org/content/367/6477/569
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fgenetics-of-schizophreni&filter=22
The genetic origins of schizophrenia
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