Genetics of schizophrenia in South African Xhosa informs understanding for all human populations

January 30, 2020

In the first genetic analysis of schizophrenia in an ancestral African population, the South African Xhosa, researchers report that individuals with schizophrenia are more likely to carry rare damaging genetic mutations than those who are well. The work informs the understanding of schizophrenia for all human populations. Critically, this study was not undertaken because the Xhosa have an unusually high prevalence of schizophrenia, but rather, because ancestral African populations - which rarely have been the focus of genetics research - harbor the most human genetic diversity. The lack of genetics studies in Africa, where nearly 99% of human evolution took place, leaves a major gap in understanding the human genome and the genetic causes of complex diseases like schizophrenia. Without studies in Africa, many generations of human genetic history are missing from scientists' understanding of human adaptation and disease. Schizophrenia, a debilitating long-term mental disorder that can significantly impact how a person thinks, feels, and behaves, is estimated to affect between 0.3-0.7% of the world's population. The illness varies genetically among patients, and in many patients involves mutations that damage genes essential to brain development. Because fewer children are born to persons with schizophrenia, very recent and de novo mutations are a major factor in its development. Suleyman Gulsuner and colleagues from the U.S. and South Africa examined the DNA sequences of all genes from more than 1,800 Xhosa individuals from South Africa, roughly half of whom had been diagnosed with schizophrenia. Individuals with schizophrenia were more likely to carry one or more rare damaging mutations, particularly in genes that function in brain synapses. Human biology is universal. The greater genetic variation in Africans provides a unique opportunity to discover and evaluate disease-associated genes that are relevant to all human populations. These discoveries can help inform new treatments.

American Association for the Advancement of Science

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