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Science. 2020 Jan 31;367(6477):569-573. doi: 10.1126/science.aay8833.

Genetics of schizophrenia in the South African Xhosa.

Author information

1
Department of Medicine, Department of Genome Sciences, and Department of Psychiatry, University of Washington, Seattle, WA, USA.
2
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
3
Mailman School of Public Health, Columbia University, New York, NY, USA.
4
New York State Psychiatric Institute, New York, NY, USA.
5
Division of Human Genetics, University of Cape Town, Cape Town, South Africa.
6
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
7
Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
8
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
9
Department of Psychology, Rhodes University, Makhanda (Grahamstown), South Africa.
10
Department of Psychiatry and Human Behavioral Sciences, Walter Sisulu University, Mthatha, South Africa.
11
Department of Medicine, Department of Genome Sciences, and Department of Psychiatry, University of Washington, Seattle, WA, USA. mcking@u.washington.edu.

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.

PMID:
32001654
DOI:
10.1126/science.aay8833

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