Genetics of schizophrenia in the South African Xhosa.

TitleGenetics of schizophrenia in the South African Xhosa.
Publication TypeJournal Article
Year of Publication2020
AuthorsGulsuner, S, Stein, DJ, Susser, ES, Sibeko, G, Pretorius, A, Walsh, T, Majara, L, Mndini, MM, Mqulwana, SG, Ntola, OA, Casadei, S, Ngqengelele, LL, Korchina, V, van der Merwe, C, Malan, M, Fader, KM, Feng, M, Willoughby, E, Muzny, DM, Baldinger, A, Andrews, HF, Gur, RC, Gibbs, RA, Zingela, Z, Nagdee, M, Ramesar, RS, King, M-C, McClellan, JM
Date Published2020 Jan 31
KeywordsAge Factors, Autistic Disorder, Bipolar Disorder, Dopamine, Female, gamma-Aminobutyric Acid, Genetic Variation, Glutamine, Humans, Male, Mutation, Neural Pathways, Schizophrenia, Sex Factors, South Africa, Synapses, Synaptic Transmission

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.

Alternate JournalScience
PubMed ID32001654
PubMed Central IDPMC9558321
Grant ListU01 MH096754 / MH / NIMH NIH HHS / United States
U01 MH096844 / MH / NIMH NIH HHS / United States
U01 MH125054 / MH / NIMH NIH HHS / United States
U01 MH096756 / MH / NIMH NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States

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