Genome-Wide Association Study of Relative Telomere Length
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 te...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091863/ |
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pubmed-3091863 |
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pubmed-30918632011-05-13 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 Research Article 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. Public Library of Science 2011-05-10 /pmc/articles/PMC3091863/ /pubmed/21573004 http://dx.doi.org/10.1371/journal.pone.0019635 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
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 |
| spellingShingle |
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 |
| author_facet |
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 |
| author_sort |
Prescott, Jennifer |
| title |
Genome-Wide Association Study of Relative Telomere Length |
| title_short |
Genome-Wide Association Study of Relative Telomere Length |
| title_full |
Genome-Wide Association Study of Relative Telomere Length |
| title_fullStr |
Genome-Wide Association Study of Relative Telomere Length |
| title_full_unstemmed |
Genome-Wide Association Study of Relative Telomere Length |
| title_sort |
genome-wide association study of relative telomere length |
| description |
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. |
| publisher |
Public Library of Science |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091863/ |
| _version_ |
1611453179783806976 |