Correction: Prenatal Tobacco Smoke Exposure Is Associated with Childhood DNA CpG Methylation

Background: Smoking while pregnant is associated with a myriad of negative health outcomes in the child. Some of the detrimental effects may be due to epigenetic modifications, although few studies have investigated this hypothesis in detail. Objectives: To characterize site-specific epigenetic modifications conferred by prenatal smoking exposure within asthmatic children. Methods: Using Illumina HumanMethylation27 microarrays, we estimated the degree of methylation at 27,578 distinct DNA sequences located primarily in gene promoters using whole blood DNA samples from the Childhood Asthma Management Program (CAMP) subset of Asthma BRIDGE childhood asthmatics (n = 527) ages 5–12 with prenatal smoking exposure data available. Using beta-regression, we screened loci for differential methylation related to prenatal smoke exposure, adjusting for gender, age and clinical site, and accounting for multiple comparisons by FDR. Results: Of 27,578 loci evaluated, 22,131 (80%) passed quality control assessment and were analyzed. Sixty-five children (12%) had a history of prenatal smoke exposure. At an FDR of 0.05, we identified 19 CpG loci significantly associated with prenatal smoke, of which two replicated in two independent populations. Exposure was associated with a 2% increase in mean CpG methylation in FRMD4A (p = 0.01) and Cllorf52 (p = 0.001) compared to no exposure. Four additional genes, XPNPEP1, PPEF2, SMPD3 and CRYGN, were nominally associated in at least one replication group. Conclusions: These data suggest that prenatal exposure to tobacco smoke is associated with reproducible epigenetic changes that persist well into childhood. However, the biological significance of these altered loci remains unknown. Citation: Breton CV, Siegmund KD, Joubert BR, Wang X, Qui W, et al. (2014) Prenatal Tobacco Smoke Exposure Is Associated with Childhood DNA CpG Methylation. PLoS ONE 9(6): e99716. doi:10.1371/journal.pone. 0099716 Editor: Angela H. Ting, Cleveland Clinic Foundation, United States of America Received February 21, 2014; Accepted May 18, 2014; Published June 25, 2014 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01 HL65899, P01 HL083069 R01 HL 086601, from the National Heart, Lung and Blood Institute, National Institutes of Health. The methylation data described here was funded by 5RC2HL101543-02 and NIEHS grants 5P30ES007048 and 1K01ES017801. Also supported in part by the Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services, US. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (contract no NO-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537-01), and the Norwegian Research Council/FUGE (grant no. 151918/S10). KCB was supported in part by the Mary Beryl Patch Turnbull Scholar Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * Email: Breton@usc.edu " Membership for extended Asthma BRIDGE consortium authorship list in File S1.