Genetics and geography of leukocyte telomere length in sub-Saharan Africans (original) (raw)
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Aging Cell, 2008
Americans have longer LTL than whites. We studied crosssectionally 2453 individuals from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study (age = = = = 30-93 years) and the Bogalusa Heart Study (age = = = = 19-37 years), comprising 1742 whites and 711 African Americans. We measured LTL by Southern blots of the terminal restriction fragments length. In 234 participants, telomere repeats were also measured by quantitative polymerase chain reaction (qPCR). Adjusted for age and body mass index (BMI), the respective leukocyte telomere lengths (mean ± ± ± ± SEM) were considerably longer in African Americans than in whites both in the Family Heart Study (7.004 ± ± ± ± 0.033 kb vs. 6.735 ± ± ± ± 0.024 kb, p < < < < 0.0001) and the Bogalusa Heart Study (7.923 ± ± ± ± 0.063 kb vs. 7.296 ± ± ± ± 0.039 kb, p < < < < 0.0001). We confirmed the racial effect on LTL by qPCR (3.038 ± ± ± ± 0.565 T/S units for African Americans vs. 2.714 ± ± ± ± 0.487 T/S units for whites, p < < < < 0.001). Cross-sectionally, sex-and BMI-adjusted LTL became shorter with age (range 19-93 years) at a steeper slope in African Americans than in whites (0.029 kb year-1 vs. 0.020 kb year-1, respectively, p = = = = 0.0001). We suggest that racial difference in LTL arises from a host of interacting biological factors, including replication rates of hematopoietic stem cells.
Shorter Telomere Length in Europeans than in Africans due to Polygenetic Adaptation
Human molecular genetics, 2016
Leukocyte telomere length (LTL), which reflects telomere length in other somatic tissues, is a complex genetic trait. Eleven SNPs have been shown in genome-wide association studies to be associated with LTL at a genome-wide level of significance within cohorts of European ancestry. It has been observed that LTL is longer in African Americans than in Europeans. The underlying reason for this difference is unknown. Here we show that LTL is significantly longer in sub-Saharan Africans than in both Europeans and African Americans. Based on the 11 LTL-associated alleles and genetic data in phase 3 of the 1000 Genomes Project, we show that the shifts in allele frequency within Europe and between Europe and Africa do not fit the pattern expected by neutral genetic drift. Our findings suggest that differences in LTL within Europeans and between Europeans and Africans is influenced by polygenic adaptation and that differences in LTL between Europeans and Africans might explain, in part, ethn...
Circulating leukocyte telomere length is highly heritable among families of Arab descent
BMC Medical Genetics, 2012
Background: Telomere length, an indicator of ageing and longevity, has been correlated with several biomarkers of cardiometabolic disease in both Arab children and adults. It is not known, however, whether or not telomere length is a highly conserved inheritable trait in this homogeneous cohort, where age-related diseases are highly prevalent. As such, the aim of this study was to address the inheritability of telomere length in Saudi families and the impact of cardiometabolic disease biomarkers on telomere length.
2021
The determinants and biomedical consequences of variation in leukocyte telomere length (LTL), a proposed marker of biological age, are only partially understood. Here we report the creation and initial characterization of LTL measurements in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ∼7 years younger in “biological age” than men. Compared to white Europeans, LTL is longer in African, Chinese and other major ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes have weaker associations. Age, ethnicity, sex and white cell count explain ∼5.5% of LTL variance. Using paired samples from 1351 participants taken ∼5 years apart, we show the regression-dilution ratio for LTL is ∼0.65. This novel resource provides major opportunities to investigate LTL and multiple biomedical phenotypes.
Nature Aging, 2022
Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in "biological age" than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal 5 age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.
Genetic Determinants of Telomere Length in African American Youth
Scientific reports, 2018
Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between 8 and 20 years old) and performed the first genome-wide association study of TL in this population. We were unable to replicate neither the 34 reported genetic associations found in adults nor the six genetic associations found in European children. However, we discovered a novel genome-wide ...
The American Journal of Human Genetics, 2006
Telomeres play a central role in cellular senescence and cancer pathobiology and are associated with age-related diseases such as atherosclerosis and dementia. Telomere length varies between individuals of the same age, is influenced by DNA-damaging factors such as oxidative stress, and is heritable. We performed a quantitative-trait linkage analysis using an ∼10-cM genomewide map for mean leukocyte terminal-restriction fragment (TRF) lengths measured by Southern blotting, in 2,050 unselected women aged 18-80 years, comprising 1,025 complete dizygotic twin pairs. Heritability of mean batch-adjusted TRF was 36% (95% confidence interval [CI] 18%-48%), with a large common environmental effect of 49% (95% CI 40%-58%). Significant linkage was observed on chromosome 14 (LOD 3.9) at 14q23.2, and suggestive linkage at 10q26.13 . This is the first report of loci, mapped in a sample of healthy individuals, that influence mean telomere variation in humans.
Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease
Pediatrics, 2016
In adults, leukocyte telomere length (LTL) is variable, familial, and longer in women and in offspring conceived by older fathers. Although short LTL is associated with atherosclerotic cardiovascular disease, long LTL is associated with major cancers. The prevailing notion is that LTL is a "telomeric clock," whose movement (expressed in LTL attrition) reflects the pace of aging. Accordingly, individuals with short LTL are considered to be biologically older than their peers. Recent studies suggest that LTL is largely determined before adulthood. We examined whether factors that largely characterize LTL in adults also influence LTL in newborns. LTL was measured in blood samples from 490 newborns and their parents. LTL (mean ± SD) was longer (9.50 ± 0.70 kb) in newborns than in their mothers (7.92 ± 0.67 kb) and fathers (7.70 ± 0.71 kb) (both P < .0001); there was no difference in the variance of LTL among the 3 groups. Newborn LTL correlated more strongly with age-adjust...
Difference in Relative Telomere Length Between Sudanese and Chinese Individuals
Iranian Red Crescent Medical Journal
Background: Racial/ethnic variations in the relative telomere length have been clearly described or infrequently studied. The relative telomere length has emerged as a biological aging marker; however, the difference in the telomere length between Sudanese and Chinese individuals is unclear. Objectives: The present study examined the difference in the relative telomere length between Sudanese and Chinese individuals. Methods: The blood samples of Sudanese and Chinese healthy individuals were randomly collected, and their deoxyribonucleic acid was obtained in this study. The relative telomere length was measured by quantitative polymerase chain reaction. The difference in the relative telomere length was analyzed using the Mann-Whitney U test. The degree of distribution in the relative telomere length was assessed using a two-sample Kolmogorov-Smirnov Z test. Results: According to the obtained results, the difference in the relative telomere length between Sudanese and Chinese indivi...