Genetics of schizophrenia in the South African Xhosa

S. Gulsuner; D. J. Stein; E. S. Susser; G. Sibeko; A. Pretorius; T. Walsh; L. Majara; M. M. Mndini; S. G. Mqulwana; O. A. Ntola; S. Casadei; L. L. Ngqengelele; V. Korchina; C. Van Der Merwe; M. Malan; K. M. Fader; M. Feng; E. Willoughby; D. Muzny; A. Baldinger; H. F. Andrews; R. C. Gur; R. A. Gibbs; Z. Zingela; M. Nagdee; R. S. Ramesar; M. C. King; J. M. McClellan

doi:10.1126/science.aay8833

Genetics of schizophrenia in the South African Xhosa

S. Gulsuner, D. J. Stein, E. S. Susser, G. Sibeko, A. Pretorius, T. Walsh, L. Majara, M. M. Mndini, S. G. Mqulwana, O. A. Ntola, S. Casadei, L. L. Ngqengelele, V. Korchina, C. Van Der Merwe, M. Malan, K. M. Fader, M. Feng, E. Willoughby, D. Muzny, A. BaldingerH. F. Andrews, R. C. Gur, R. A. Gibbs, Z. Zingela, M. Nagdee, R. S. Ramesar, M. C. King^*, J. M. McClellan

^*Corresponding author for this work

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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, g-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.

Original language	English
Pages (from-to)	569-573
Number of pages	5
Journal	Science
Volume	367
Issue number	6477
DOIs	https://doi.org/10.1126/science.aay8833
State	Published - 31 Jan 2020
Externally published	Yes

Funding

Funders	Funder number
National Institute of Mental Health	U01MH096756

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Gulsuner, S., Stein, D. J., Susser, E. S., Sibeko, G., Pretorius, A., Walsh, T., Majara, L., Mndini, M. M., Mqulwana, S. G., Ntola, O. A., Casadei, S., Ngqengelele, L. L., Korchina, V., Van Der Merwe, C., Malan, M., Fader, K. M., Feng, M., Willoughby, E., Muzny, D., ... McClellan, J. M. (2020). Genetics of schizophrenia in the South African Xhosa. Science, 367(6477), 569-573. https://doi.org/10.1126/science.aay8833

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title = "Genetics of schizophrenia in the South African Xhosa",

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, g-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.",

author = "S. Gulsuner and Stein, {D. J.} and Susser, {E. S.} and G. Sibeko and A. Pretorius and T. Walsh and L. Majara and Mndini, {M. M.} and Mqulwana, {S. G.} and Ntola, {O. A.} and S. Casadei and Ngqengelele, {L. L.} and V. Korchina and {Van Der Merwe}, C. and M. Malan and Fader, {K. M.} and M. Feng and E. Willoughby and D. Muzny and A. Baldinger and Andrews, {H. F.} and Gur, {R. C.} and Gibbs, {R. A.} and Z. Zingela and M. Nagdee and Ramesar, {R. S.} and King, {M. C.} and McClellan, {J. M.}",

year = "2020",

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doi = "10.1126/science.aay8833",

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Gulsuner, 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, D, Baldinger, A, Andrews, HF, Gur, RC, Gibbs, RA, Zingela, Z, Nagdee, M, Ramesar, RS, King, MC & McClellan, JM 2020, 'Genetics of schizophrenia in the South African Xhosa', Science, vol. 367, no. 6477, pp. 569-573. https://doi.org/10.1126/science.aay8833

TY - JOUR

T1 - Genetics of schizophrenia in the South African Xhosa

AU - Gulsuner, S.

AU - Stein, D. J.

AU - Susser, E. S.

AU - Sibeko, G.

AU - Pretorius, A.

AU - Walsh, T.

AU - Majara, L.

AU - Mndini, M. M.

AU - Mqulwana, S. G.

AU - Ntola, O. A.

AU - Casadei, S.

AU - Ngqengelele, L. L.

AU - Korchina, V.

AU - Van Der Merwe, C.

AU - Malan, M.

AU - Fader, K. M.

AU - Feng, M.

AU - Willoughby, E.

AU - Muzny, D.

AU - Baldinger, A.

AU - Andrews, H. F.

AU - Gur, R. C.

AU - Gibbs, R. A.

AU - Zingela, Z.

AU - Nagdee, M.

AU - Ramesar, R. S.

AU - King, M. C.

AU - McClellan, J. M.

PY - 2020/1/31

Y1 - 2020/1/31

N2 - 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, g-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.

AB - 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, g-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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SN - 0036-8075

VL - 367

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EP - 573

JO - Science

JF - Science

IS - 6477

ER -

Genetics of schizophrenia in the South African Xhosa

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