The association of telomere length and genetic variation in telomere biology genes

Lisa Mirabello, Kai Yu, Peter Kraft, Immaculata De Vivo, David J. Hunter, Jennifer Prescott, Jason Y.Y. Wong, Nilanjan Chatterjee, Richard B. Hayes, Sharon A. Savage

Research output: Contribution to journalArticle

Abstract

Telomeres cap chromosome ends and are critical for genomic stability. Many telomere-associated proteins are important for telomere length maintenance. Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in genes encoding telomere-associated proteins (RTEL1 and TERT-CLPTM1) as markers of cancer risk. We conducted an association study of telomere length and 743 SNPs in 43 telomere biology genes. Telomere length in peripheral blood DNA was determined by Q-PCR in 3,646 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Nurses' Health Study. We investigated associations by SNP, gene, and pathway (functional group). We found no associations between telomere length and SNPs in TERT-CLPTM1L or RTEL1. Telomere length was not significantly associated with specific functional groups. Thirteen SNPs from four genes (MEN1, MRE11A, RECQL5, and TNKS) were significantly associated with telomere length. The strongest findings were in MEN1 (gene-based P=0.006), menin, which associates with the telomerase promoter and may negatively regulate telomerase. This large association study did not find strong associations with telomere length. The combination of limited diversity and evolutionary conservation suggest that these genes may be under selective pressure. More work is needed to explore the role of genetic variants in telomere length regulation.

Original languageEnglish (US)
Pages (from-to)1050-1058
Number of pages9
JournalHuman mutation
Volume31
Issue number9
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Keywords

  • Epidemiology
  • SNP
  • Single nucleotide polymorphism
  • Telomere biology
  • Telomere length

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    Mirabello, L., Yu, K., Kraft, P., De Vivo, I., Hunter, D. J., Prescott, J., Wong, J. Y. Y., Chatterjee, N., Hayes, R. B., & Savage, S. A. (2010). The association of telomere length and genetic variation in telomere biology genes. Human mutation, 31(9), 1050-1058. https://doi.org/10.1002/humu.21314