Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs.
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 approximate 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 (LOD 2.4) and 3p26.1 (LOD 2.7). This is the first report of loci, mapped in a sample of healthy individuals, that influence mean telomere variation in humans.
Andrew
Toby
T
Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, London SE1 7EH, United Kingdom. toby.andrew@kcl.ac.uk
Aviv
Abraham
A
Falchi
Mario
M
Surdulescu
Gabriela L
GL
Gardner
Jeffrey P
JP
Lu
Xiaobin
X
Kimura
Masayuki
M
Kato
Bernet S
BS
Valdes
Ana M
AM
Spector
Tim D
TD
D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D035781:Siblings; D016615:Telomere / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics*