Association between telomere length and Plasmodium falciparum malaria endemicity in sub-Saharan Africans

• DOI: 10.1016/j.ajhg.2024.04.003
• Publication Date: 2024-05-02T14:37:41Z
• Authors: Michael A. McQuillan; Simon Verhulst; Matthew E.B. Hansen; William Beggs; Dawit Wolde Meskel; Gurja Belay; Thomas Nyambo; Sununguko Wata Mp...; Gaonyadiwe George...; Charles Fokunang; Alfred K. Njamnshi; Stephen J. Chanock; Abraham Aviv; Sarah A. Tishkoff
• Keywords: Adult; Male; telomere; Botswana; Endemic Diseases; Sub-Saharan African People; Plasmodium falciparum; malaria; population genetics; Black People; Telomere Homeostasis; Middle Aged; Telomere; Tanzania; Young Adult; Southern African People; Africa; Leukocytes; Humans; Female; Cameroon; Malaria, Falciparum; Africa South of the Sahara

Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.