Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation.
Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation.
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DOI：
10.1186/s12864-018-4652-7
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发表时间：
2018-04-25
期刊：
影响因子：
4.4
通讯作者：
Rietschel M
中科院分区：
文献类型：
--
作者：
Witt SH;Frank J;Gilles M;Lang M;Treutlein J;Streit F;Wolf IAC;Peus V;Scharnholz B;Send TS;Heilmann-Heimbach S;Sivalingam S;Dukal H;Strohmaier J;Sütterlin M;Arloth J;Laucht M;Nöthen MM;Deuschle M;Rietschel M
吸烟对成年人和怀孕期间吸烟母亲的后代有严重的不良健康后果。怀孕期间吸烟最广泛报道的影响之一是降低出生体重，这反过来又与成年后的慢性病有关。全表观基因组关联研究表明，吸烟者表现出一种典型的“吸烟甲基化模式”，最近有作者提出DNA甲基化介导了母亲吸烟对出生体重的影响。本研究的目的是重复先前关于甲基化介导母亲吸烟对出生体重影响的报道，并首次调查所观察到的中介效应是否具有性别特异性，以便解释甲基化水平的已知性别特异性差异。使用Illumina HumanMethylation450K头芯片测定了313名新生儿脐带血中的甲基化水平。在文献证据的基础上选择了5527个CpG位点进行了检测。为了确定观察到的母亲吸烟与出生体重之间的关联是否可归因于甲基化，对重要的CpG位点进行了中介分析。然后分别对男性和女性进行分析。经过质量控制，282名新生儿最终留在了分析中。共有25位母亲在怀孕期间一直吸烟。母亲在怀孕期间吸烟的新生儿的出生体重减少了150克。经多次检测校正，30个CpGs在母体吸烟亚组中出现差异甲基化，包括“吸烟甲基化模式”的顶级基因AHRR、MYO1G、GFI1、CYP1A1和CNTNAP2。母亲吸烟对出生体重的影响部分是由cg25325512 （PIM1）甲基化介导的；cg25949550 (CNTNAP2);cg08699196 （ITGB7）。性别特异性分析显示cg25949550 （CNTNAP2）在男性新生儿中的中介作用。目前的数据重复了先前的发现，甲基化可以介导母亲吸烟对出生体重的影响。性别依赖的中介效应分析表明，新生儿的性别可能有影响。有必要进行更大规模的研究，以调查已确定的差异甲基化位点和新生儿性别在孕妇怀孕期间吸烟与出生体重之间的关联中所起的作用。本文的在线版本（10.1186/s12864-018-4652-7）包含补充材料，授权用户可使用。
Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic “smoking methylation pattern”, and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top “smoking methylation pattern” genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight. The online version of this article (10.1186/s12864-018-4652-7) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Horikoshi, Momoko;Beaumont, Robin N.;Day, Felix R.;Warrington, Nicole M.;Kooijman, Marjolein N.;Fernandez-Tajes, Juan;Feenstra, Bjarke;van Zuydam, Natalie R.;Gaulton, Kyle J.;Grarup, Niels;Bradfield, Jonathan P.;Strachan, David P.;Li-Gao, Ruifang;Ahluwalia, Tarunveer S.;Kreiner, Eskil;Rueedi, Rico;Lyytikainen, Leo-Pekka;Cousminer, Diana L.;Wu, Ying;Thiering, Elisabeth;Wang, Carol A.;Have, Christian T.;Hottenga, Jouke-Jan;Vilor-Tejedor, Natalia;Joshi, Peter K.;Boh, Eileen Tai Hui;Ntalla, Ioanna;Pitkanen, Niina;Mahajan, Anubha;van Leeuwen, Elisabeth M.;Joro, Raimo;Lagou, Vasiliki;Nodzenski, Michael;Diver, Louise A.;Zondervan, Krina T.;Bustamante, Mariona;Marques-Vidal, Pedro;Mercader, Josep M.;Bennett, Amanda J.;Rahmioglu, Nilufer;Nyholt, Dale R.;Ma, Ronald C. W.;Tam, Claudia H. T.;Tam, Wing Hung;Ganesh, Santhi K.;van Rooij, Frank J. A.;Jones, Samuel E.;Loh, Po-Ru;Ruth, Katherine S.;Tuke, Marcus A.;Tyrrell, Jessica;Wood, Andrew R.;Yaghootkar, Hanieh;Scholtens, Denise M.;Paternoster, Lavinia;Prokopenko, Inga;Kovacs, Peter;Atalay, Mustafa;Willems, Sara M.;Panoutsopoulou, Kalliope;Wang, Xu;Carstensen, Lisbeth;Geller, Frank;Schraut, Katharina E.;Murcia, Mario;van Beijsterveldt, Catharina E. M.;Willemsen, Gonneke;Appel, Emil V. R.;Fonvig, Cilius E.;Trier, Caecilie;Tiesler, Carla M. T.;Standl, Marie;Kutalik, Zoltan;Bonas-Guarch, Silvia;Hougaard, David M.;Sanchez, Friman;Torrents, David;Waage, Johannes;Hollegaard, Mads V.;de Haan, Hugoline G.;Rosendaal, Frits R.;Medina-Gomez, Carolina;Ring, Susan M.;Hemani, Gibran;McMahon, George;Robertson, Neil R.;Groves, Christopher J.;Langenberg, Claudia;Luan, Jian'an;Scott, Robert A.;Zhao, Jing Hua;Mentch, Frank D.;MacKenzie, Scott M.;Reynolds, Rebecca M.;Lowe, William L.;Toenjes, Anke;Stumvoll, Michael;Lindi, Virpi;Lakka, Timo A.;van Duijn, Cornelia M.;Kiess, Wieland;Koerner, Antje;Sorensen, Thorkild I. A.;Niinikoski, Harri;Pahkala, Katja;Raitakari, Olli T.;Zeggini, Eleftheria;Dedoussis, George V.;Teo, Yik-Ying;Saw, Seang-Mei;Melbye, Mads;Campbell, Harry;Wilson, James F.;Vrijheid, Martine;de Geus, Eco J. C. N.;Boomsma, Dorret I.;Kadarmideen, Haja N.;Holm, Jens-Christian;Hansen, Torben;Sebert, Sylvain;Hattersley, Andrew T.;Beilin, Lawrence J.;Newnham, John P.;Pennell, Craig E.;Heinrich, Joachim;Adair, Linda S.;Borja, Judith B.;Mohlke, Karen L.;Eriksson, Johan G.;Widen, Elisabeth;Kahonen, Mika;Viikari, Jorma S.;Lehtimaki, Terho;Vollenweider, Peter;Bonnelykke, Klaus;Bisgaard, Hans;Mook-Kanamori, Dennis O.;Hofman, Albert;Rivadeneira, Fernando;Uitterlinden, Andre G.;Pisinger, Charlotta;Pedersen, Oluf;Power, Christine;Hyppoenen, Elina;Wareham, Nicholas J.;Hakonarson, Hakon;Davies, Eleanor;Walker, Brian R.;Jaddoe, Vincent W. V.;Jaervelin, Marjo-Riitta;Grant, Struan F. A.;Vaag, Allan A.;Lawlor, Debbie A.;Frayling, Timothy M.;Smith, George Davey;Morris, Andrew P.;Ong, Ken K.;Felix, Janine F.;Timpson, Nicholas J.;Perry, John R. B.;Evans, David M.;McCarthy, Mark I.;Freathy, Rachel M.
通讯作者：
Freathy, Rachel M.
影响因子：
7.6
作者：
BARON, RM;KENNY, DA
通讯作者：
KENNY, DA
影响因子：
3.7
作者：
Comuzzie AG;Cole SA;Laston SL;Voruganti VS;Haack K;Gibbs RA;Butte NF
通讯作者：
Butte NF
影响因子：
7
作者：
Imai, Kosuke;Keele, Luke;Tingley, Dustin
通讯作者：
Tingley, Dustin
在子宫内暴露于烟草的新生儿中的DNA甲基化模式。
影响因子：
7.4
作者：
Ivorra C;Fraga MF;Bayón GF;Fernández AF;Garcia-Vicent C;Chaves FJ;Redon J;Lurbe E
通讯作者：
Lurbe E