Genome-wide association study of relative telomere length

Jennifer Prescott, Peter Kraft, Daniel I. Chasman, Sharon A. Savage, Lisa Mirabello, Sonja I. Berndt, Joel L. Weissfeld, Jiali Han, Richard B. Hayes, Stephen J. Chanock, David J. Hunter, Immaculata de Vivo

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = -0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed.

Original languageEnglish (US)
Article numbere19635
JournalPLoS One
Volume6
Issue number5
DOIs
StatePublished - May 17 2011
Externally publishedYes

Fingerprint

Genome-Wide Association Study
telomeres
Telomere
Genes
Genome
loci
Health
genome
prostatic neoplasms
Single Nucleotide Polymorphism
nurses
Prostatic Neoplasms
genotyping
Alleles
Telomere Homeostasis
Nurses
National Cancer Institute (U.S.)
alleles
Human Chromosomes
Women's Health

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Prescott, J., Kraft, P., Chasman, D. I., Savage, S. A., Mirabello, L., Berndt, S. I., ... de Vivo, I. (2011). Genome-wide association study of relative telomere length. PLoS One, 6(5), [e19635]. https://doi.org/10.1371/journal.pone.0019635

Genome-wide association study of relative telomere length. / Prescott, Jennifer; Kraft, Peter; Chasman, Daniel I.; Savage, Sharon A.; Mirabello, Lisa; Berndt, Sonja I.; Weissfeld, Joel L.; Han, Jiali; Hayes, Richard B.; Chanock, Stephen J.; Hunter, David J.; de Vivo, Immaculata.

In: PLoS One, Vol. 6, No. 5, e19635, 17.05.2011.

Research output: Contribution to journalArticle

Prescott, J, Kraft, P, Chasman, DI, Savage, SA, Mirabello, L, Berndt, SI, Weissfeld, JL, Han, J, Hayes, RB, Chanock, SJ, Hunter, DJ & de Vivo, I 2011, 'Genome-wide association study of relative telomere length', PLoS One, vol. 6, no. 5, e19635. https://doi.org/10.1371/journal.pone.0019635
Prescott J, Kraft P, Chasman DI, Savage SA, Mirabello L, Berndt SI et al. Genome-wide association study of relative telomere length. PLoS One. 2011 May 17;6(5). e19635. https://doi.org/10.1371/journal.pone.0019635
Prescott, Jennifer ; Kraft, Peter ; Chasman, Daniel I. ; Savage, Sharon A. ; Mirabello, Lisa ; Berndt, Sonja I. ; Weissfeld, Joel L. ; Han, Jiali ; Hayes, Richard B. ; Chanock, Stephen J. ; Hunter, David J. ; de Vivo, Immaculata. / Genome-wide association study of relative telomere length. In: PLoS One. 2011 ; Vol. 6, No. 5.
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