Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs

Toby Andrew, Abraham Aviv, Mario Falchi, Gabriela L Surdulescu, Jeffrey P Gardner, Xiaobin Lu, Masayuki Kimura, Bernet S Kato, Ana M Valdes, Tim D Spector

Research output: Contribution to journalArticlepeer-review

224 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)480-6
Number of pages7
JournalAmerican Journal of Human Genetics
Volume78
Issue number3
DOIs
Publication statusPublished - Mar 2006

Keywords

  • Chromosome Mapping
  • Chromosomes, Human
  • Female
  • Humans
  • Leukocytes
  • Polymorphism, Restriction Fragment Length
  • Quantitative Trait Loci
  • Quantitative Trait, Heritable
  • Siblings
  • Telomere
  • Twins, Dizygotic

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