Journal article

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

Thomas Battram, Rebecca C Richmond, Laura Baglietto, Philip C Haycock, Vittorio Perduca, Stig E Bojesen, Tom R Gaunt, Gibran Hemani, Florence Guida, Robert Carreras-Torres, Rayjean Hung, Christopher Amos, Joshua R Freeman, Torkjel M Sandanger, Therese H Nost, Borge G Nordestgaard, Andrew E Teschendorff, Silvia Polidoro, Paolo Vineis, Gianluca Severi Show all

International Journal of Epidemiology | OXFORD UNIV PRESS | Published : 2019

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 fro..

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Grants

Awarded by Wellcome Trust


Awarded by Cancer Research UK


Awarded by UK Medical Research Council


Awarded by Wellcome


Awarded by UK BBSRC


Funding Acknowledgements

This work was partly supported by a Wellcome Trust PhD studentship to T.B. (203746); and by Cancer Research UK (C18281/A19169, C57854/A22171 and C52724/A20138). This work was also supported by the UK Medical Research Council (MC_UU_00011/1 and MC_UU_00011/5), which funds a Unit at the University of Bristol where T.B., R.C.R., P.C.H., T.R.G., G.D.S. and C.L.R. work. Funding to pay the Open Access publication charges for this article was provided by the University of Bristol RCUK. The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Methylation data in the ALSPAC cohort were generated as part of the UK BBSRC-funded (BB/I025751/1 and BB/I025263/1) Accessible Resource for Integrated Epigenomic Studies (ARIES) [http://www.ariesepigenomics.org.uk].