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A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk

Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the “iCOGS” custom genotyping array. All ∼200...

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Main Authors: Pooley, Karen A. (Author) , Bojesen, Stig E. (Author) , Weischer, Maren (Author) , Nielsen, Sune F. (Author) , Thompson, Deborah (Author) , Amin Al Olama, Ali (Author) , Michailidou, Kyriaki (Author) , Tyrer, Jonathan P. (Author) , Benlloch, Sara (Author) , Brown, Judith (Author) , Audley, Tina (Author) , Luben, Robert (Author) , Khaw, K-T (Author) , Neal, David E. (Author) , Hamdy, Freddie C. (Author) , Donovan, Jenny L. (Author) , Kote-Jarai, Zsofia (Author) , Baynes, Caroline (Author) , Shah, Mitul (Author) , Bolla, Manjeet K. (Author) , Wang, Qin (Author) , Dennis, Joe (Author) , Dicks, Ed (Author) , Yang, Rongxi (Author) , Rudolph, Anja (Author) , Schildkraut, Joellen (Author) , Chang-Claude, Jenny (Author) , Burwinkel, Barbara (Author) , Chenevix-Trench, Georgia (Author) , Pharoah, Paul D. P. (Author) , Berchuck, Andrew (Author) , Eeles, Rosalind A. (Author) , Easton, Douglas F. (Author) , Dunning, Alison M. (Author) , Nordestgaard, Børge G. (Author)
Format: Article (Journal)
Language:English
Published: July 29, 2013
In: Human molecular genetics
Year: 2013, Volume: 22, Issue: 24, Pages: 5056-5064
ISSN:1460-2083
DOI:10.1093/hmg/ddt355
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/hmg/ddt355
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/hmg/article/22/24/5056/569757
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Author Notes:Karen A. Pooley, Stig E. Bojesen, Maren Weischer, Sune F. Nielsen, Deborah Thompson, Ali Amin Al Olama, Kyriaki Michailidou, Jonathan P. Tyrer, Sara Benlloch, Judith Brown, Tina Audley, Robert Luben, K-T Khaw, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Zsofia Kote-Jarai, Caroline Baynes, Mitul Shah, Manjeet K. Bolla, Qin Wang, Joe Dennis, Ed Dicks, Rongxi Yang, Anja Rudolph, Joellen Schildkraut, Jenny Chang-Claude, Barbara Burwinkel, Georgia Chenevix-Trench, Paul D. P. Pharoah, Andrew Berchuck, Rosalind A. Eeles, Douglas F. Easton, Alison M. Dunning, Børge G. Nordestgaard
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Summary:Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the “iCOGS” custom genotyping array. All ∼200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL association (Ptrend < 4 × 10−10) at 3p14.4 close to PXK and evidence (Ptrend < 7 × 10−7) for TL loci at 6p22.1 (ZNF311) and 20q11.2 (BCL2L1). We additionally confirmed (Ptrend < 5 × 10−14) the previously reported loci at 3q26.2 (TERC), 5p15.3 (TERT) and 10q24.3 (OBFC1) and found supportive evidence (Ptrend < 5 × 10−4) for the published loci at 2p16.2 (ACYP2), 4q32.2 (NAF1) and 20q13.3 (RTEL1). SNPs tagging these loci explain TL differences of up to 731 bp (corresponding to 18% of total TL in healthy individuals), however, they display little direct evidence for association with breast, ovarian or prostate cancer risks.
Item Description:Gesehen am 06.12.2021
Physical Description:Online Resource
ISSN:1460-2083
DOI:10.1093/hmg/ddt355

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