Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa

Deepti Gurdasani; Tommy Carstensen; Segun Fatumo; Guanjie Chen; Chris S. Franklin; Javier Prado-martinez; Heleen Bouman; Federico Abascal; Marc Haber; Ioanna Tachmazidou; Iain Mathieson; Kenneth Ekoru; Marianne K. Degorter; Rebecca N. Nsubuga; Chris Finan; Eleanor Wheeler; Li Chen; David N. Cooper; Stephan Schiffels; Yuan Chen; Graham R.s. Ritchie; Martin O. Pollard; Mary D. Fortune; Alex J. Mentzer; Erik Garrison; Anders Bergström; Konstantinos Hatzikotoulas; Adebowale Adeyemo; Ayo Doumatey; Heather Elding; Louise V. Wain; Georg Ehret; Paul L. Auer; Charles L. Kooperberg; Alexander P. Reiner; Nora Franceschini; Dermot Maher; Stephen B. Montgomery; Carl Kadie; Chris Widmer; Yali Xue; Janet Seeley; Gershim Asiki; Anatoli Kamali; Elizabeth H. Young; Cristina Pomilla; Nicole Soranzo; Eleftheria Zeggini; Fraser Pirie; Andrew P. Morris; David Heckerman; Chris Tyler-smith; Ayesha A. Motala; Charles Rotimi; Pontiano Kaleebu; Inês Barroso; Manj S. Sandhu

doi:10.1016/j.cell.2019.10.004

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa

Deepti Gurdasani, Tommy Carstensen, Segun Fatumo, Guanjie Chen, Chris S. Franklin, Javier Prado-martinez, Heleen Bouman, Federico Abascal, Marc Haber, Ioanna Tachmazidou, Iain Mathieson, Kenneth Ekoru, Marianne K. Degorter, Rebecca N. Nsubuga, Chris Finan, Eleanor Wheeler, Li Chen, David N. Cooper, Stephan Schiffels, Yuan ChenGraham R.s. Ritchie, Martin O. Pollard, Mary D. Fortune, Alex J. Mentzer, Erik Garrison, Anders Bergström, Konstantinos Hatzikotoulas, Adebowale Adeyemo, Ayo Doumatey, Heather Elding, Louise V. Wain, Georg Ehret, Paul L. Auer, Charles L. Kooperberg, Alexander P. Reiner, Nora Franceschini, Dermot Maher, Stephen B. Montgomery, Carl Kadie, Chris Widmer, Yali Xue, Janet Seeley, Gershim Asiki, Anatoli Kamali, Elizabeth H. Young, Cristina Pomilla, Nicole Soranzo, Eleftheria Zeggini, Fraser Pirie, Andrew P. Morris, David Heckerman, Chris Tyler-smith, Ayesha A. Motala, Charles Rotimi, Pontiano Kaleebu, Inês Barroso, Manj S. Sandhu

Division of Musculoskeletal & Dermatological Sciences (L5)

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Abstract

Genomic studies in African populations provide unique opportunities to understand disease aetiology, human diversity and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals, and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically-correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans is best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, haematological, lipid and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

Original language	English
Pages (from-to)	984-1002.e36
Journal	Cell
Volume	179
Issue number	4
Early online date	31 Oct 2019
DOIs	https://doi.org/10.1016/j.cell.2019.10.004
Publication status	Published - 31 Oct 2019

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10.1016/j.cell.2019.10.004

UGP_24.09.19Accepted author manuscript, 894 KBLicence: CC BY-NC-ND

https://linkinghub.elsevier.com/retrieve/pii/S0092867419311201

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Gurdasani, D., Carstensen, T., Fatumo, S., Chen, G., Franklin, C. S., Prado-martinez, J., Bouman, H., Abascal, F., Haber, M., Tachmazidou, I., Mathieson, I., Ekoru, K., Degorter, M. K., Nsubuga, R. N., Finan, C., Wheeler, E., Chen, L., Cooper, D. N., Schiffels, S., ... Sandhu, M. S. (2019). Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa. Cell, 179(4), 984-1002.e36. https://doi.org/10.1016/j.cell.2019.10.004

@article{7995e91a9f9b4248a76f4e54c3cc4183,

title = "Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa",

abstract = "Genomic studies in African populations provide unique opportunities to understand disease aetiology, human diversity and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals, and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically-correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans is best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, haematological, lipid and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.",

author = "Deepti Gurdasani and Tommy Carstensen and Segun Fatumo and Guanjie Chen and Franklin, {Chris S.} and Javier Prado-martinez and Heleen Bouman and Federico Abascal and Marc Haber and Ioanna Tachmazidou and Iain Mathieson and Kenneth Ekoru and Degorter, {Marianne K.} and Nsubuga, {Rebecca N.} and Chris Finan and Eleanor Wheeler and Li Chen and Cooper, {David N.} and Stephan Schiffels and Yuan Chen and Ritchie, {Graham R.s.} and Pollard, {Martin O.} and Fortune, {Mary D.} and Mentzer, {Alex J.} and Erik Garrison and Anders Bergstr{\"o}m and Konstantinos Hatzikotoulas and Adebowale Adeyemo and Ayo Doumatey and Heather Elding and Wain, {Louise V.} and Georg Ehret and Auer, {Paul L.} and Kooperberg, {Charles L.} and Reiner, {Alexander P.} and Nora Franceschini and Dermot Maher and Montgomery, {Stephen B.} and Carl Kadie and Chris Widmer and Yali Xue and Janet Seeley and Gershim Asiki and Anatoli Kamali and Young, {Elizabeth H.} and Cristina Pomilla and Nicole Soranzo and Eleftheria Zeggini and Fraser Pirie and Morris, {Andrew P.} and David Heckerman and Chris Tyler-smith and Motala, {Ayesha A.} and Charles Rotimi and Pontiano Kaleebu and In{\^e}s Barroso and Sandhu, {Manj S.}",

year = "2019",

month = oct,

day = "31",

doi = "10.1016/j.cell.2019.10.004",

language = "English",

volume = "179",

pages = "984--1002.e36",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier BV",

number = "4",

}

Gurdasani, D, Carstensen, T, Fatumo, S, Chen, G, Franklin, CS, Prado-martinez, J, Bouman, H, Abascal, F, Haber, M, Tachmazidou, I, Mathieson, I, Ekoru, K, Degorter, MK, Nsubuga, RN, Finan, C, Wheeler, E, Chen, L, Cooper, DN, Schiffels, S, Chen, Y, Ritchie, GRS, Pollard, MO, Fortune, MD, Mentzer, AJ, Garrison, E, Bergström, A, Hatzikotoulas, K, Adeyemo, A, Doumatey, A, Elding, H, Wain, LV, Ehret, G, Auer, PL, Kooperberg, CL, Reiner, AP, Franceschini, N, Maher, D, Montgomery, SB, Kadie, C, Widmer, C, Xue, Y, Seeley, J, Asiki, G, Kamali, A, Young, EH, Pomilla, C, Soranzo, N, Zeggini, E, Pirie, F, Morris, AP, Heckerman, D, Tyler-smith, C, Motala, AA, Rotimi, C, Kaleebu, P, Barroso, I & Sandhu, MS 2019, 'Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa', Cell, vol. 179, no. 4, pp. 984-1002.e36. https://doi.org/10.1016/j.cell.2019.10.004

TY - JOUR

T1 - Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa

AU - Gurdasani, Deepti

AU - Carstensen, Tommy

AU - Fatumo, Segun

AU - Chen, Guanjie

AU - Franklin, Chris S.

AU - Prado-martinez, Javier

AU - Bouman, Heleen

AU - Abascal, Federico

AU - Haber, Marc

AU - Tachmazidou, Ioanna

AU - Mathieson, Iain

AU - Ekoru, Kenneth

AU - Degorter, Marianne K.

AU - Nsubuga, Rebecca N.

AU - Finan, Chris

AU - Wheeler, Eleanor

AU - Chen, Li

AU - Cooper, David N.

AU - Schiffels, Stephan

AU - Chen, Yuan

AU - Ritchie, Graham R.s.

AU - Pollard, Martin O.

AU - Fortune, Mary D.

AU - Mentzer, Alex J.

AU - Garrison, Erik

AU - Bergström, Anders

AU - Hatzikotoulas, Konstantinos

AU - Adeyemo, Adebowale

AU - Doumatey, Ayo

AU - Elding, Heather

AU - Wain, Louise V.

AU - Ehret, Georg

AU - Auer, Paul L.

AU - Kooperberg, Charles L.

AU - Reiner, Alexander P.

AU - Franceschini, Nora

AU - Maher, Dermot

AU - Montgomery, Stephen B.

AU - Kadie, Carl

AU - Widmer, Chris

AU - Xue, Yali

AU - Seeley, Janet

AU - Asiki, Gershim

AU - Kamali, Anatoli

AU - Young, Elizabeth H.

AU - Pomilla, Cristina

AU - Soranzo, Nicole

AU - Zeggini, Eleftheria

AU - Pirie, Fraser

AU - Morris, Andrew P.

AU - Heckerman, David

AU - Tyler-smith, Chris

AU - Motala, Ayesha A.

AU - Rotimi, Charles

AU - Kaleebu, Pontiano

AU - Barroso, Inês

AU - Sandhu, Manj S.

PY - 2019/10/31

Y1 - 2019/10/31

N2 - Genomic studies in African populations provide unique opportunities to understand disease aetiology, human diversity and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals, and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically-correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans is best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, haematological, lipid and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

AB - Genomic studies in African populations provide unique opportunities to understand disease aetiology, human diversity and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals, and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically-correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans is best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, haematological, lipid and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

U2 - 10.1016/j.cell.2019.10.004

DO - 10.1016/j.cell.2019.10.004

M3 - Article

SN - 0092-8674

VL - 179

SP - 984-1002.e36

JO - Cell

JF - Cell

IS - 4

ER -

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa

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