Genetics and geography of leukocyte telomere length in sub-Saharan Africans

Steven C Hunt; Matthew E B Hansen; Simon Verhulst; Michael A McQuillan; William Beggs; Tsung-Po Lai; Gaonyadiwe G Mokone; Sununguko Wata Mpoloka; Dawit Wolde Meskel; Gurja Belay; Thomas B Nyambo; Christian C Abnet; Meredith Yeager; Stephen J Chanock; Michael A Province; Scott M Williams; Abraham Aviv; Sarah A Tishkoff

doi:10.1093/hmg/ddaa187

Genetics and geography of leukocyte telomere length in sub-Saharan Africans

Hum Mol Genet. 2020 Nov 4;29(18):3014-3020. doi: 10.1093/hmg/ddaa187.

Authors

Steven C Hunt¹, Matthew E B Hansen², Simon Verhulst³, Michael A McQuillan², William Beggs², Tsung-Po Lai⁴, Gaonyadiwe G Mokone⁵, Sununguko Wata Mpoloka⁶, Dawit Wolde Meskel⁷, Gurja Belay⁷, Thomas B Nyambo⁸, Christian C Abnet⁹, Meredith Yeager⁹, Stephen J Chanock⁹, Michael A Province¹⁰, Scott M Williams¹¹, Abraham Aviv⁴, Sarah A Tishkoff^{2

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Affiliations

¹ Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar.
² Department of Genetics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
³ Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.
⁴ Center of Human Development and Aging, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, 07103, USA.
⁵ Faculty of Medicine, Department of Biomedical Sciences, University of Botswana, Gaborone, Botswana.
⁶ Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
⁷ Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia.
⁸ Department of Biochemistry, Kampala International University, Tanzania.
⁹ Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20892,USA.
¹⁰ Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, 63108, USA.
¹¹ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
¹² Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Abstract

Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African-Americans (AAms) and 2464 European-Americans (EAms). LTL differed significantly across SSAs (P = 0.003), with the San from Botswana (with the oldest genomic ancestry) having the longest LTL and populations from Ethiopia having the shortest LTL. SSAs had significantly longer LTL than AAms [P = 6.5(e-16)] whose LTL was significantly longer than EAms [P = 2.5(e-7)]. Genetic variation in SSAs explained 52% of LTL variance versus 27% in AAms and 34% in EAms. Adjustment for genetic variation removed the LTL differences among SSAs. LTL genetic variation among SSAs, with the longest LTL in the San, supports the hypothesis that longer LTL was ancestral in humans. Identifying factors driving LTL variation in Africa may have important ramifications for LTL-associated diseases.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Africa South of the Sahara / epidemiology
Black People / genetics
Black or African American / genetics
Cardiovascular Diseases / blood
Cardiovascular Diseases / epidemiology
Cardiovascular Diseases / genetics*
Female
Humans
Leukocytes / pathology
Male
Middle Aged
Neoplasms / blood
Neoplasms / epidemiology
Neoplasms / genetics*
Phylogeography
Telomere / genetics*
Telomere Homeostasis / genetics*
White People / genetics

Abstract

Publication types

MeSH terms

Grants and funding