Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa

Elizabeth G Atkinson; Shareefa Dalvie; Yakov Pichkar; Allan Kalungi; Lerato Majara; Anne Stevenson; Tamrat Abebe; Dickens Akena; Melkam Alemayehu; Fred K Ashaba; Lukoye Atwoli; Mark Baker; Lori B Chibnik; Nicole Creanza; Mark J Daly; Abebaw Fekadu; Bizu Gelaye; Stella Gichuru; Wilfred E Injera; Roxanne James; Symon M Kariuki; Gabriel Kigen; Nastassja Koen; Karestan C Koenen; Zan Koenig; Edith Kwobah; Joseph Kyebuzibwa; Henry Musinguzi; Rehema M Mwema; Benjamin M Neale; Carter P Newman; Charles R J C Newton; Linnet Ongeri; Sohini Ramachandran; Raj Ramesar; Welelta Shiferaw; Dan J Stein; Rocky E Stroud; Solomon Teferra; Mary T Yohannes; Zukiswa Zingela; Alicia R Martin; NeuroGAP-Psychosis Study Team

doi:10.1016/j.ajhg.2022.07.013

Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa

Am J Hum Genet. 2022 Sep 1;109(9):1667-1679. doi: 10.1016/j.ajhg.2022.07.013.

Authors

Elizabeth G Atkinson¹, Shareefa Dalvie², Yakov Pichkar³, Allan Kalungi⁴, Lerato Majara⁵, Anne Stevenson⁶, Tamrat Abebe⁷, Dickens Akena⁸, Melkam Alemayehu⁹, Fred K Ashaba¹⁰, Lukoye Atwoli¹¹, Mark Baker¹², Lori B Chibnik¹³, Nicole Creanza³, Mark J Daly¹⁴, Abebaw Fekadu¹⁵, Bizu Gelaye¹⁶, Stella Gichuru¹⁷, Wilfred E Injera¹⁸, Roxanne James¹⁹, Symon M Kariuki²⁰, Gabriel Kigen²¹, Nastassja Koen², Karestan C Koenen¹⁶, Zan Koenig¹², Edith Kwobah¹⁷, Joseph Kyebuzibwa⁸, Henry Musinguzi¹⁰, Rehema M Mwema²², Benjamin M Neale¹⁴, Carter P Newman¹⁶, Charles R J C Newton²⁰, Linnet Ongeri²², Sohini Ramachandran²³, Raj Ramesar²⁴, Welelta Shiferaw⁹, Dan J Stein², Rocky E Stroud¹⁶, Solomon Teferra⁹, Mary T Yohannes¹², Zukiswa Zingela²⁵, Alicia R Martin¹⁴; NeuroGAP-Psychosis Study Team

Affiliations

¹ Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: elizabeth.atkinson@bcm.edu.
² Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
³ Department of Biological Sciences and Evolutionary Studies Initiative, Vanderbilt University, Nashville, TN, USA.
⁴ Department of Psychiatry, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; Mental Health Section of MRC/UVRI & LSHTM Uganda Research Unit, Entebbe, Uganda.
⁵ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; South African Medical Research Council (SAMRC) Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁶ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁷ Department of Microbiology, Immunology, and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
⁸ Department of Psychiatry, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
⁹ Department of Psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
¹⁰ Department of Immunology & Molecular Biology, College of Health Sciences, Makerere University, Kampala, Uganda.
¹¹ Department of Mental Health, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya; Brain and Mind Institute and Department of Internal Medicine, Medical College East Africa, the Aga Khan University, Nairobi, Kenya.
¹² Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
¹⁴ Analytic and Translational Genetics Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁵ Department of Psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Centre for Innovative Drug Development & Therapeutic Trials for Africa, Addis Ababa University, Addis Ababa, Ethiopia.
¹⁶ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
¹⁷ Department of Mental Health, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.
¹⁸ Department of Immunology, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.
¹⁹ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
²⁰ Neurosciences Unit, Clinical Department, KEMRI-Wellcome Trust Research Programme-Coast, Kilifi, Kenya; Department of Psychiatry, University of Oxford, Oxford, UK.
²¹ Department of Pharmacology and Toxicology, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.
²² Neurosciences Unit, Clinical Department, KEMRI-Wellcome Trust Research Programme-Coast, Kilifi, Kenya.
²³ Department of Ecology and Evolutionary Biology and Center for Computational Molecular Biology, Brown University, Providence, RI, USA.
²⁴ South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
²⁵ Executive Dean's Office, Faculty of Health Sciences, Nelson Mandela University, Port Elizabeth, South Africa.

Abstract

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.

Keywords: Africa; diverse populations; genotypes; linguistics; population genetics; population structure.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Africa, Southern
Black People / genetics
Genetic Structures
Genetic Variation* / genetics
Genetics, Population*
Humans

Abstract

Publication types

MeSH terms

Grants and funding