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Appraising the causal relevance of DNA methylation for risk of lung cancer

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Harvard

Battram, T, Richmond, RC, Baglietto, L, Haycock, PC, Perduca, V, Bojesen, SE, Gaunt, TR, Hemani, G, Guida, F, Carreras-Torres, R, Hung, R, Amos, CI, Freeman, JR, Sandanger, TM, Nøst, TH, Nordestgaard, BG, Teschendorff, AE, Polidoro, S, Vineis, P, Severi, G, Hodge, AM, Giles, GG, Grankvist, K, Johansson, MB, Johansson, M, Davey Smith, G & Relton, CL 2019, 'Appraising the causal relevance of DNA methylation for risk of lung cancer' International Journal of Epidemiology, bind 48, nr. 5, s. 1493-1504. https://doi.org/10.1093/ije/dyz190

APA

Battram, T., Richmond, R. C., Baglietto, L., Haycock, P. C., Perduca, V., Bojesen, S. E., ... Relton, C. L. (2019). Appraising the causal relevance of DNA methylation for risk of lung cancer. International Journal of Epidemiology, 48(5), 1493-1504. https://doi.org/10.1093/ije/dyz190

CBE

Battram T, Richmond RC, Baglietto L, Haycock PC, Perduca V, Bojesen SE, Gaunt TR, Hemani G, Guida F, Carreras-Torres R, Hung R, Amos CI, Freeman JR, Sandanger TM, Nøst TH, Nordestgaard BG, Teschendorff AE, Polidoro S, Vineis P, Severi G, Hodge AM, Giles GG, Grankvist K, Johansson MB, Johansson M, Davey Smith G, Relton CL. 2019. Appraising the causal relevance of DNA methylation for risk of lung cancer. International Journal of Epidemiology. 48(5):1493-1504. https://doi.org/10.1093/ije/dyz190

MLA

Vancouver

Author

Battram, Thomas ; Richmond, Rebecca C ; Baglietto, Laura ; Haycock, Philip C ; Perduca, Vittorio ; Bojesen, Stig E ; Gaunt, Tom R ; Hemani, Gibran ; Guida, Florence ; Carreras-Torres, Robert ; Hung, Rayjean ; Amos, Christopher I ; Freeman, Joshua R ; Sandanger, Torkjel M ; Nøst, Therese H ; Nordestgaard, Børge G ; Teschendorff, Andrew E ; Polidoro, Silvia ; Vineis, Paolo ; Severi, Gianluca ; Hodge, Allison M ; Giles, Graham G ; Grankvist, Kjell ; Johansson, Mikael B ; Johansson, Mattias ; Davey Smith, George ; Relton, Caroline L. / Appraising the causal relevance of DNA methylation for risk of lung cancer. I: International Journal of Epidemiology. 2019 ; Bind 48, Nr. 5. s. 1493-1504.

Bibtex

@article{c0470ed7be744a5796dba4687fdcfc6f,
title = "Appraising the causal relevance of DNA methylation for risk of lung cancer",
abstract = "BACKGROUND: DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated.METHODS: We first performed a meta-analysis of four epigenome-wide association studies (EWAS) of lung cancer (918 cases, 918 controls). Next, we conducted a two-sample Mendelian randomization analysis, using genetic instruments for methylation at CpG sites identified in the EWAS meta-analysis, and 29 863 cases and 55 586 controls from the TRICL-ILCCO lung cancer consortium, to appraise the possible causal role of methylation at these sites on lung cancer.RESULTS: Sixteen CpG sites were identified from the EWAS meta-analysis [false discovery rate (FDR) < 0.05], for 14 of which we could identify genetic instruments. Mendelian randomization provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites plays a causal role in lung cancer development (FDR > 0.05), including for cg05575921-AHRR where methylation is strongly associated with both smoke exposure and lung cancer risk.CONCLUSIONS: The results contrast with previous observational and mediation analysis, which have made strong claims regarding the causal role of DNA methylation. Thus, previous suggestions of a mediating role of methylation at sites identified in peripheral blood, such as cg05575921-AHRR, could be unfounded. However, this study does not preclude the possibility that differential DNA methylation at other sites is causally involved in lung cancer development, especially within lung tissue.",
author = "Thomas Battram and Richmond, {Rebecca C} and Laura Baglietto and Haycock, {Philip C} and Vittorio Perduca and Bojesen, {Stig E} and Gaunt, {Tom R} and Gibran Hemani and Florence Guida and Robert Carreras-Torres and Rayjean Hung and Amos, {Christopher I} and Freeman, {Joshua R} and Sandanger, {Torkjel M} and N{\o}st, {Therese H} and Nordestgaard, {B{\o}rge G} and Teschendorff, {Andrew E} and Silvia Polidoro and Paolo Vineis and Gianluca Severi and Hodge, {Allison M} and Giles, {Graham G} and Kjell Grankvist and Johansson, {Mikael B} and Mattias Johansson and {Davey Smith}, George and Relton, {Caroline L}",
note = "{\circledC} The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.",
year = "2019",
month = "10",
day = "1",
doi = "10.1093/ije/dyz190",
language = "English",
volume = "48",
pages = "1493--1504",
journal = "International Journal of Epidemiology",
issn = "0300-5771",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Appraising the causal relevance of DNA methylation for risk of lung cancer

AU - Battram, Thomas

AU - Richmond, Rebecca C

AU - Baglietto, Laura

AU - Haycock, Philip C

AU - Perduca, Vittorio

AU - Bojesen, Stig E

AU - Gaunt, Tom R

AU - Hemani, Gibran

AU - Guida, Florence

AU - Carreras-Torres, Robert

AU - Hung, Rayjean

AU - Amos, Christopher I

AU - Freeman, Joshua R

AU - Sandanger, Torkjel M

AU - Nøst, Therese H

AU - Nordestgaard, Børge G

AU - Teschendorff, Andrew E

AU - Polidoro, Silvia

AU - Vineis, Paolo

AU - Severi, Gianluca

AU - Hodge, Allison M

AU - Giles, Graham G

AU - Grankvist, Kjell

AU - Johansson, Mikael B

AU - Johansson, Mattias

AU - Davey Smith, George

AU - Relton, Caroline L

N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - BACKGROUND: DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated.METHODS: We first performed a meta-analysis of four epigenome-wide association studies (EWAS) of lung cancer (918 cases, 918 controls). Next, we conducted a two-sample Mendelian randomization analysis, using genetic instruments for methylation at CpG sites identified in the EWAS meta-analysis, and 29 863 cases and 55 586 controls from the TRICL-ILCCO lung cancer consortium, to appraise the possible causal role of methylation at these sites on lung cancer.RESULTS: Sixteen CpG sites were identified from the EWAS meta-analysis [false discovery rate (FDR) < 0.05], for 14 of which we could identify genetic instruments. Mendelian randomization provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites plays a causal role in lung cancer development (FDR > 0.05), including for cg05575921-AHRR where methylation is strongly associated with both smoke exposure and lung cancer risk.CONCLUSIONS: The results contrast with previous observational and mediation analysis, which have made strong claims regarding the causal role of DNA methylation. Thus, previous suggestions of a mediating role of methylation at sites identified in peripheral blood, such as cg05575921-AHRR, could be unfounded. However, this study does not preclude the possibility that differential DNA methylation at other sites is causally involved in lung cancer development, especially within lung tissue.

AB - BACKGROUND: DNA methylation changes in peripheral blood have recently been identified in relation to lung cancer risk. Some of these changes have been suggested to mediate part of the effect of smoking on lung cancer. However, limitations with conventional mediation analyses mean that the causal nature of these methylation changes has yet to be fully elucidated.METHODS: We first performed a meta-analysis of four epigenome-wide association studies (EWAS) of lung cancer (918 cases, 918 controls). Next, we conducted a two-sample Mendelian randomization analysis, using genetic instruments for methylation at CpG sites identified in the EWAS meta-analysis, and 29 863 cases and 55 586 controls from the TRICL-ILCCO lung cancer consortium, to appraise the possible causal role of methylation at these sites on lung cancer.RESULTS: Sixteen CpG sites were identified from the EWAS meta-analysis [false discovery rate (FDR) < 0.05], for 14 of which we could identify genetic instruments. Mendelian randomization provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites plays a causal role in lung cancer development (FDR > 0.05), including for cg05575921-AHRR where methylation is strongly associated with both smoke exposure and lung cancer risk.CONCLUSIONS: The results contrast with previous observational and mediation analysis, which have made strong claims regarding the causal role of DNA methylation. Thus, previous suggestions of a mediating role of methylation at sites identified in peripheral blood, such as cg05575921-AHRR, could be unfounded. However, this study does not preclude the possibility that differential DNA methylation at other sites is causally involved in lung cancer development, especially within lung tissue.

U2 - 10.1093/ije/dyz190

DO - 10.1093/ije/dyz190

M3 - Journal article

VL - 48

SP - 1493

EP - 1504

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

IS - 5

ER -

ID: 59307644