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 BollaQin 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

Department of Clinical Medicine

94 Citations (Scopus)

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
Journal	Human Molecular Genetics
Volume	22
Issue number	24
Pages (from-to)	5056-5064
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddt355
Publication status	Published - Dec 2013

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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. https://doi.org/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. / Pooley, Karen A; Bojesen, Stig E; Weischer, Maren et al.
In: Human Molecular Genetics, Vol. 22, No. 24, 12.2013, p. 5056-5064.

Research output: Contribution to journal › Journal article › Research › peer-review

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, K-T, 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, pp. 5056-5064. https://doi.org/10.1093/hmg/ddt355

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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 ~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 K-T Khaw 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}",

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doi = "10.1093/hmg/ddt355",

language = "English",

volume = "22",

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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.

U2 - 10.1093/hmg/ddt355

DO - 10.1093/hmg/ddt355

M3 - Journal article

SN - 0964-6906

VL - 22

SP - 5056

EP - 5064

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 24

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

Abstract

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