Appraising the causal relevance of DNA methylation for risk of lung cancer
文献类型：期刊论文
| 作者 | Battram, Thomas1,2; Richmond, Rebecca C.1,2; Haycock, Philip C.1,2; Gaunt, Tom R.1,2; Hemani, Gibran1,2; Smith, George Davey1,2; Relton, Caroline L.1,2; Baglietto, Laura3; Perduca, Vittorio4; Bojesen, Stig E.5,6,7 |
| 刊名 | INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
 |
| 出版日期 | 2019 |
| 卷号 | 48期号:5页码:1493-1504 |
| 关键词 | Lung cancer DNA methylation Mendelian randomization ALSPAC ARIES |
| ISSN号 | 0300-5771 |
| DOI | 10.1093/ije/dyz190 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| 学科主题 | Materials Science |
| WOS关键词 | MENDELIAN RANDOMIZATION ; SMOKING ; ASSOCIATION ; BIAS ; INSTRUMENTS ; EFFICIENT ; DESIGN ; LOCI |
| 语种 | 英语 |
| CSCD记录号 | CSCD:31549173 |
| WOS记录号 | WOS:000501732200019 |
| 出版者 | OXFORD UNIV PRESS |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1199]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England; 2.Univ Bristol, Populat Hlth Sci, Bristol, Avon, England; 3.Univ Pisa, Dept Clin & Expt Med, Pisa, Italy; 4.Univ Paris 05, Lab Math Appl, Paris, France; 5.Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark; 6.Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark; 7.Copenhagen Univ Hosp, Frederiksberg Hosp, Copenhagen City Heart Study, Copenhagen, Denmark; 8.Int Agcy Res Canc, Genet Epidemiol Div, Lyon, France; 9.Sinai Hlth Syst, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada; 10.Dartmouth Coll, Biomed Data Sci, Geisel Sch Med, Hanover, NH 03755 USA; |
| 推荐引用方式 GB/T 7714 | Battram, Thomas,Richmond, Rebecca C.,Haycock, Philip C.,et al. Appraising the causal relevance of DNA methylation for risk of lung cancer[J]. INTERNATIONAL JOURNAL OF EPIDEMIOLOGY,2019,48(5):1493-1504. |
| APA | Battram, Thomas.,Richmond, Rebecca C..,Haycock, Philip C..,Gaunt, Tom R..,Hemani, Gibran.,...&,.(2019).Appraising the causal relevance of DNA methylation for risk of lung cancer.INTERNATIONAL JOURNAL OF EPIDEMIOLOGY,48(5),1493-1504. |
| MLA | Battram, Thomas,et al."Appraising the causal relevance of DNA methylation for risk of lung cancer".INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 48.5(2019):1493-1504. |
入库方式： OAI收割
来源：上海营养与健康研究所
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