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

被引：130

作者：

Gurdasani, Deepti ^{[1
]}

Carstensen, Tommy ^{[2
]}

Fatumo, Segun ^{[3
,4
,5
,6
]}

Chen, Guanjie ^{[7
]}

Franklin, Chris S. ^{[2
]}

Prado-Martinez, Javier ^{[2
]}

Bouman, Heleen ^{[2
]}

Abascal, Federico ^{[2
]}

Haber, Marc ^{[2
]}

Tachmazidou, Ioanna ^{[2
]}

Mathieson, Iain ^{[8
]}

Ekoru, Kenneth ^{[9
]}

DeGorter, Marianne K. ^{[10
]}

Nsubuga, Rebecca N. ^{[9
]}

Finan, Chris ^{[2
]}

Wheeler, Eleanor ^{[2
]}

Chen, Li ^{[2
]}

Cooper, David N. ^{[11
]}

Schiffels, Stephen ^{[12
]}

Chen, Yuan ^{[2
]}

Ritchie, Graham R. S. ^{[2
]}

Pollard, Martin O. ^{[2
]}

Fortune, Mary D. ^{[2
]}

Mentzer, Alex J. ^{[13
]}

Garrison, Erik ^{[2
]}

Bergstrom, Anders ^{[2
]}

Hatzikotoulas, Konstantinos ^{[2
]}

Adeyemo, Adebowale ^{[7
]}

Doumatey, Ayo ^{[7
]}

Elding, Heather ^{[2
]}

Wain, Louise V. ^{[14
,15
]}

Ehret, George ^{[16
,17
]}

Auer, Paul L. ^{[18
]}

Kooperberg, Charles L. ^{[19
]}

Reiner, Alexander P. ^{[20
,21
]}

Franceschini, Nora ^{[22
]}

Maher, Dermot P. ^{[9
]}

Montgomery, Stephen B. ^{[8
,23
]}

Kadie, Carl ^{[24
]}

Widmer, Chris ^{[25
]}

Xue, Yali ^{[2
]}

Seeley, Janet ^{[3
,9
]}

Asiki, Gershim ^{[9
]}

Kamali, Anatoli ^{[9
]}

Young, Elizabeth H. ^{[2
,26
]}

Pomilla, Cristina ^{[2
,26
]}

Soranzo, Nicole ^{[2
,27
,28
]}

Zeggini, Eleftheria ^{[29
]}

Pirie, Fraser ^{[30
]}

Morris, Andrew P. ^{[13
,31
]}

机构：

[1] Queen Marys Univ London, William Harvey Res Inst, London, England

[2] Wellcome Sanger Inst, Cambridge, England

[3] London Sch Hyg & Trop Med, London, England

[4] UMIC, MRC UVRI, Entebbe, Uganda

[5] LSHTM Uganda Res Unit, Entebbe, Uganda

[6] Natl Biotechnol Dev Agcy CGRI NABDA, CGRI, H3Africa Bioinformat Network H3ABioNet Node, Abuja, Nigeria

[7] NIH, Ctr Res Genom & Global Hlth, Bldg 10, Bethesda, MD 20892 USA

[8] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[9] UVRI, MRC, Uganda Res Unit AIDS, Entebbe, Uganda

[10] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[11] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff, S Glam, Wales

[12] Max Planck Inst Sci Human Hist, Dept Archaeogenet, Jena, Germany

[13] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[14] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England

[15] Glenfield Hosp, Leicester Biomed Res Ctr, Natl Inst Hlth Res, Leicester, Leics, England

[16] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[17] Geneva Univ Hosp, Rue Gabrielle Perret Gentil 4, CH-1211 Geneva 14, Switzerland

[18] Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA

[19] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[20] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[21] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[22] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[23] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[24] Microsoft Res, Redmond, CA USA

[25] Microsoft Res, Los Angeles, CA USA

[26] Univ Cambridge, Dept Med, Cambridge, England

[27] Univ Cambridge, Dept Haematol, Cambridge, England

[28] Univ Cambridge, Natl Inst Hlth Res Blood & Transplant Unit NIHR B, Cambridge, England

[29] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Translat Genom, Neuherberg, Germany

[30] Univ KwaZulu Natal, Dept Diabet & Endocrinol, Durban, South Africa

[31] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England

[32] Univ Cambridge, MRC Epidemiol Unit, Cambridge, England

来源：

CELL | 2019年 / 179卷 / 04期

基金：

美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金;

关键词：

OMRON M6 HEM-7001-E; DENSITY-LIPOPROTEIN CHOLESTEROL; SINGLE-NUCLEOTIDE POLYMORPHISMS; APPROVED RECOMMENDATION 1985; MULTIPLE-TESTING CORRECTION; PRESSURE MEASURING DEVICE; WIDE ASSOCIATION; INTERNATIONAL PROTOCOL; NATURAL-SELECTION; BLOOD-PRESSURE;

D O I：

10.1016/j.cell.2019.10.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genomic studies in African populations provide unique opportunities to understand disease etiology, 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 was 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, hematological, 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.

引用

页码：984 / +

页数：55

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