Faculty Collaboration Database

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa. Cell 2019 Oct 31;179(4):984-1002.e36

Date

11/02/2019

Pubmed ID

31675503

Pubmed Central ID

PMC7202134

DOI

10.1016/j.cell.2019.10.004

Scopus ID

2-s2.0-85074135187 (requires institutional sign-in at Scopus site)   108 Citations

Abstract

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.

Author List

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

Author

Paul L. Auer PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Female
Gene Frequency
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Genomics
Humans
Male
Polymorphism, Single Nucleotide
Uganda
Whole Genome Sequencing