Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

被引:51
作者
Everson, Todd M. [1 ]
Vives-Usano, Marta [2 ,3 ,4 ]
Seyve, Emie [5 ]
Cardenas, Andres [6 ,7 ]
Lacasana, Marina [4 ,8 ,9 ]
Craig, Jeffrey M. [10 ,11 ,12 ]
Lesseur, Corina [13 ]
Baker, Emily R. [14 ]
Fernandez-Jimenez, Nora [15 ,16 ,17 ]
Heude, Barbara [18 ]
Perron, Patrice [19 ]
Gonzalez-Alzaga, Beatriz [8 ,9 ]
Halliday, Jane [11 ,20 ]
Deyssenroth, Maya A. [13 ]
Karagas, Margaret R. [21 ]
Iniguez, Carmen [4 ,22 ,23 ]
Bouchard, Luigi [24 ]
Carmona-Saez, Pedro [25 ,26 ]
Loke, Yuk J. [10 ,11 ]
Hao, Ke [27 ]
Belmonte, Thalia [28 ]
Charles, Marie A. [18 ]
Martorell-Marugan, Jordi [25 ,29 ]
Muggli, Evelyne [11 ,20 ]
Chen, Jia [13 ]
Fernandez, Mariana F. [4 ,9 ,30 ,31 ]
Tost, Jorg [32 ]
Gomez-Martin, Antonio [33 ]
London, Stephanie J. [34 ]
Sunyer, Jordi [3 ,4 ,35 ,36 ]
Marsit, Carmen J. [1 ,37 ]
Lepeule, Johanna [5 ]
Hivert, Marie-France [6 ,38 ]
Bustamante, Mariona [2 ,3 ,4 ,35 ]
机构
[1] Emory Univ, Gangarosa Dept Environm Hlth, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA
[2] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain
[3] Univ Pompeu Fabra, Barcelona, Spain
[4] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain
[5] Univ Grenoble Alpes, IAB, CNRS, INSERM, Grenoble, France
[6] Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA 02115 USA
[7] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA
[8] Andalusian Sch Publ Hlth, Granada, Spain
[9] Inst Invest Biosantaria IbsGRANADA, Granada, Spain
[10] Murdoch Childrens Res Inst, Epigenet Grp, Parkville, Vic, Australia
[11] Univ Melbourne, Dept Paediat, Parkville, Vic, Australia
[12] Deakin Univ, IMPACT Inst Mental & Phys Hlth & Clin Translat, Geelong, Vic, Australia
[13] Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA
[14] Dartmouth Coll, Dept Obstet & Gynecol, Geisel Sch Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA
[15] Univ Basque Country UPV EHU, Leioa, Spain
[16] Biocruces Bizkaia Hlth Res Inst, Baracaldo, Spain
[17] Basque Govt, Publ Hlth Div Gipuzkoa, San Sebastian, Spain
[18] Univ Paris, INSERM, CRESS, INRAE, Paris, France
[19] Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada
[20] Murdoch Childrens Res Inst, Reprod Epidemiol, Parkville, Vic, Australia
[21] Dartmouth Coll, Geisel Sch Med, Dept Epidemiol, Hanover, NH 03755 USA
[22] Univ Valencia, Dept Stat & Computat Res, Valencia, Spain
[23] Univ Valencia, Epidemiol & Environm Hlth Joint Res Unit, FISABIO,Univ Jaume I, Val Ncia, Spain
[24] Univ Sherbrooke, Dept Biochem & Funct Genom, Sherbrooke, PQ, Canada
[25] Univ Granada, GENYO Ctr Genom & Oncol Res, Bioinformat Unit, Andalusian Reg Govt,Pfizer, Granada, Spain
[26] Univ Granada, Fac Sci, Dept Stat, Granada, Spain
[27] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA
[28] Univ Oviedo, IUOPA, Oviedo, Spain
[29] Atrys Hlth SA, Barcelona, Spain
[30] Univ Granada, Biomed Res Ctr CIBM, Granada, Spain
[31] Univ Granada, Sch Med, Granada, Spain
[32] CEA Inst Biol Francois Jacob, Ctr Natl Rech Genom Humaine, Lab Epigenet & Environm, Evry, France
[33] Univ Granada, GENYO Ctr Genom & Oncol Res, Genom Unit, Andalusian Reg Govt,Pfizer, Granada, Spain
[34] NIEHS, Div Intramural Res, NIH, US Dept HHS, Durham, NC USA
[35] Barcelona Inst Global Hlth, ISGlobal, Barcelona, Spain
[36] Hosp del Mar Med Res Inst IMIM, Barcelona, Spain
[37] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA
[38] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA
关键词
BIRTH-WEIGHT; GENE-EXPRESSION; FACTOR RECEPTOR; COHORT PROFILE; TROPHOBLAST; NEWBORNS; ASSOCIATIONS; EXPOSURE; HYPOXIA; LENGTH;
D O I
10.1038/s41467-021-24558-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Maternal smoking during pregnancy contributes to poor birth outcomes. Here the authors perform a meta-analysis of the associations between maternal smoking during pregnancy and placental DNA methylation and identify links between these and poor birth outcomes, which may better inform the mechanisms through which smoking impacts placental function and fetal growth. Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.
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页数:13
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