Genetics of schizophrenia in the South African Xhosa

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Science  31 Jan 2020:
Vol. 367, Issue 6477, pp. 569-573
DOI: 10.1126/science.aay8833

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African schizophrenia genetic variants

The genetics of schizophrenia have predominately been studied in populations of European and Asian descent. However, studies in Africans, who host the greatest degree of human genetic diversity, have lagged. Examining the exomes of more than 1800 Xhosa individuals from South Africa, about half of which have been diagnosed with schizophrenia, Gulsuner et al. identified both rare and common genetic variants associated with the disease. They found that the genetic architecture of schizophrenia in Africans generally reflects that of Europeans but that the greater genetic variation in Africa provides more power to detect relationships of genes to phenotypes.

Science, this issue p. 569


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.

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