Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.
Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.
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具有跨种族影响的烟草吸烟的新DNA甲基化特征。
DOI：
10.1186/s13148-021-01018-4
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发表时间：
2021-02-16
影响因子：
5.7
通讯作者：
Bell JT
中科院分区：
文献类型：
--
作者：
Christiansen C;Castillo-Fernandez JE;Domingo-Relloso A;Zhao W;El-Sayed Moustafa JS;Tsai PC;Maddock J;Haack K;Cole SA;Kardia SLR;Molokhia M;Suderman M;Power C;Relton C;Wong A;Kuh D;Goodman A;Small KS;Smith JA;Tellez-Plaza M;Navas-Acien A;Ploubidis GB;Hardy R;Bell JT
吸烟仍然是可预防的主要死因之一。吸烟在血液甲基化组上留下了强烈的签名，如使用Infinium HumanMethylation 450 BeadChip的多项研究所示。在这里，我们探索了Illumina MethylationEPIC BeadChip（EPIC）阵列上的新型血液甲基化吸烟信号，该阵列还针对增强子中的新型CpG位点。使用EPIC DNA甲基化谱对来自四个英国人群队列的1407份血液样本进行了吸烟甲基化荟萃分析，包括MRC国家健康与发展调查（NSHD）或1946年英国出生队列，国家儿童发育研究（NCDS）或1958年出生队列，1970年英国队列研究（BCS 70）和TwinsUK队列（TwinsUK）。总体发现样本包括269名当前吸烟者，497名前吸烟者和643名从不吸烟者。在3425个跨种族样本中进行复制，包括1989-1991年参加强心研究（SHS）的2325名美国印第安人和1100名非洲裔美国人参加动脉病遗传流行病学网络研究（GENOA）。在Bonferroni校正后，吸烟者和从不吸烟者之间总共500个基因中的952个CpG位点的甲基化差异。有526个新的吸烟相关的CpG位点仅由EPIC阵列分析，其中486个（92%）在美国印第安人和非洲裔美国人样本的荟萃分析中重复。新的CpG位点映射到含有先前确定的吸烟甲基化信号的基因和80个先前未与吸烟相关的新基因，其中SLAMF 7中的新信号最强。比较前与从不吸烟者发现，这些网站中的37个持续差异甲基化后停止，其中16个代表新的信号，只描绘了EPIC阵列。我们观察到吸烟相关信号的CpG岛和增强子区域的富集，与以前的结果一致的耗尽。这项研究确定了新的吸烟相关信号作为暴露于吸烟的可能生物标志物，并可能有助于提高我们对吸烟相关疾病风险的理解。
Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989–1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.
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影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
--
作者：
Ishibashi, Mariko;Soeda, Saori;Tamura, Hideto
通讯作者：
Tamura, Hideto
影响因子：
8
作者：
Bloch, M.;Ousingsawat, J.;Bubendorf, L.
通讯作者：
Bubendorf, L.
影响因子：
4.4
作者：
Lu, Ling-Min;Zavitz, Caleb C. J.;Stampfli, Martin R.
通讯作者：
Stampfli, Martin R.
影响因子：
--
作者：
Fortin, Jean-Philippe;Fertig, Elana;Hansen, Kasper
通讯作者：
Hansen, Kasper