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

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

doi:10.1093/hmg/ddt355

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

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

Research output: Contribution to journal › Article › peer-review

122 Scopus citations

Abstract

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 (P_trend < 4 × 10^-10) at 3p14.4 close to PXK and evidence (P_trend < 7 × 10^-7) for TL loci at 6p22.1 (ZNF311) and 20q11.2 (BCL2L1). We additionally confirmed (P_trend < 5 × 10^-14) the previously reported loci at 3q26.2 (TERC), 5p15.3 (TERT) and 10q24.3 (OBFC1) and found supportive evidence (P_trend < 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.

Original language	English
Article number	ddt355
Pages (from-to)	5056-5064
Number of pages	9
Journal	Human Molecular Genetics
Volume	22
Issue number	24
DOIs	https://doi.org/10.1093/hmg/ddt355
State	Published - Dec 2013
Externally published	Yes

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Pooley, K. A., Bojesen, S. E., Weischer, M., Nielsen, S. F., Thompson, D., Amin Al Olama, A., Michailidou, K., Tyrer, J. P., Benlloch, S., Brown, J., Audley, T., Luben, R., Khaw, K. T., Neal, D. E., Hamdy, F. C., Donovan, J. L., Kote-Jarai, Z., Baynes, C., Shah, M., ... Nordestgaard, B. G. (2013). A genome-wide association scan (GWAS) for mean telomere length within the COGS project: Identified loci show little association with hormone-related cancer risk. Human Molecular Genetics, 22(24), 5056-5064. Article ddt355. https://doi.org/10.1093/hmg/ddt355

@article{ff1487ff67164829bc6a141d1a2fec6c,

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

abstract = "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 \textasciitilde{}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.",

author = "Pooley, \{Karen A.\} and Bojesen, \{Stig E.\} and Maren Weischer and Nielsen, \{Sune F.\} and Deborah Thompson and \{Amin Al Olama\}, Ali and Kyriaki Michailidou and Tyrer, \{Jonathan P.\} and Sara Benlloch and Judith Brown and Tina Audley and Robert Luben and Khaw, \{K. T.\} and Neal, \{David E.\} and Hamdy, \{Freddie C.\} and Donovan, \{Jenny L.\} and Zsofia Kote-Jarai and Caroline Baynes and Mitul Shah and Bolla, \{Manjeet K.\} and Qin Wang and Joe Dennis and Ed Dicks and Rongxi Yang and Anja Rudolph and Joellen Schildkraut and Jenny Chang-Claude and Barbara Burwinkel and Georgia Chenevix-Trench and Pharoah, \{Paul D.P.\} and Andrew Berchuck and Eeles, \{Rosalind A.\} and Easton, \{Douglas F.\} and Dunning, \{Alison M.\} and Nordestgaard, \{B{\o}rge G.\}",

year = "2013",

month = dec,

doi = "10.1093/hmg/ddt355",

language = "Ingl{\'e}s",

volume = "22",

pages = "5056--5064",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "24",

}

Pooley, KA, Bojesen, SE, Weischer, M, Nielsen, SF, Thompson, D, Amin Al Olama, A, Michailidou, K, Tyrer, JP, Benlloch, S, Brown, J, Audley, T, Luben, R, Khaw, KT, Neal, DE, Hamdy, FC, Donovan, JL, Kote-Jarai, Z, Baynes, C, Shah, M, Bolla, MK, Wang, Q, Dennis, J, Dicks, E, Yang, R, Rudolph, A, Schildkraut, J, Chang-Claude, J, Burwinkel, B, Chenevix-Trench, G, Pharoah, PDP, Berchuck, A, Eeles, RA, Easton, DF, Dunning, AM & Nordestgaard, BG 2013, 'A genome-wide association scan (GWAS) for mean telomere length within the COGS project: Identified loci show little association with hormone-related cancer risk', Human Molecular Genetics, vol. 22, no. 24, ddt355, pp. 5056-5064. https://doi.org/10.1093/hmg/ddt355

TY - JOUR

T1 - A genome-wide association scan (GWAS) for mean telomere length within the COGS project

T2 - Identified loci show little association with hormone-related cancer risk

AU - Pooley, Karen A.

AU - Bojesen, Stig E.

AU - Weischer, Maren

AU - Nielsen, Sune F.

AU - Thompson, Deborah

AU - Amin Al Olama, Ali

AU - Michailidou, Kyriaki

AU - Tyrer, Jonathan P.

AU - Benlloch, Sara

AU - Brown, Judith

AU - Audley, Tina

AU - Luben, Robert

AU - Khaw, K. T.

AU - Neal, David E.

AU - Hamdy, Freddie C.

AU - Donovan, Jenny L.

AU - Kote-Jarai, Zsofia

AU - Baynes, Caroline

AU - Shah, Mitul

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Dicks, Ed

AU - Yang, Rongxi

AU - Rudolph, Anja

AU - Schildkraut, Joellen

AU - Chang-Claude, Jenny

AU - Burwinkel, Barbara

AU - Chenevix-Trench, Georgia

AU - Pharoah, Paul D.P.

AU - Berchuck, Andrew

AU - Eeles, Rosalind A.

AU - Easton, Douglas F.

AU - Dunning, Alison M.

AU - Nordestgaard, Børge G.

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84888147064

U2 - 10.1093/hmg/ddt355

DO - 10.1093/hmg/ddt355

M3 - Artículo

C2 - 23900074

AN - SCOPUS:84888147064

SN - 0964-6906

VL - 22

SP - 5056

EP - 5064

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 24

M1 - ddt355

ER -

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

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