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Genome-wide association study of relative telomere length

Prescott, J and Kraft, P and Chasman, DI and Savage, SA and Mirabello, L and Berndt, SI and Weissfeld, JL and Han, J and Hayes, RB and Chanock, SJ and Hunter, DJ and de Vivo, I (2011) Genome-wide association study of relative telomere length. PLoS ONE, 6 (5).

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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.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
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
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorDube, Marie-PierreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 17 May 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0019635
Refereed: Yes
MeSH Headings: Aged; Female; Genetic Loci--genetics; Genome-Wide Association Study; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide--genetics; Reproducibility of Results; Telomere--metabolism
Other ID: NLM PMC3091863
PubMed Central ID: PMC3091863
PubMed ID: 21573004
Date Deposited: 29 Aug 2012 21:11
Last Modified: 29 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/13833

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