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

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.

Figure 1

Association of leukocyte telomere length (LTL) with age for each ancestry (adjusted for sex). Linear regression lines of age versus LTL for each inferred ancestry are superimposed over the individual observations (N = 1295).

Figure 2

Sex differences in leukocyte telomere length (LTL) by ancestry (adjusted for age). Error bars are standard errors of the mean (N = 1295).

Figure 3

Leukocyte telomere length (LTL) by ancestry. LTL is shown adjusted for age and sex, and adjusted for age, sex and LTL genetic variance. The genetic variance–covariance structure of LTL was estimated using a kinship matrix calculated from identity-by-decent probabilities and using the estimated additive genetic variance, both derived using a genome-wide single-nucleotide polymorphisms array. Error bars are standard errors of the least square means (N = 1295).