title: Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs.
abstract: 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.
authors.affiliation: Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, London SE1 7EH, United Kingdom. toby.andrew@kcl.ac.uk
authors.forename: Toby
authors.initials: T
authors.lastname: Andrew
authors.forename: Abraham
authors.initials: A
authors.lastname: Aviv
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.forename: Gabriela L
authors.initials: GL
authors.lastname: Surdulescu
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Gardner
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Lu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kimura
authors.forename: Bernet S
authors.initials: BS
authors.lastname: Kato
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
mesh_terms: 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*