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{"title"=>"Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation", "type"=>"journal", "authors"=>[{"first_name"=>"Carrie V.", "last_name"=>"Breton", "scopus_author_id"=>"13905662200"}, {"first_name"=>"Kimberly D.", "last_name"=>"Siegmund", "scopus_author_id"=>"7003665798"}, {"first_name"=>"Bonnie R.", "last_name"=>"Joubert", "scopus_author_id"=>"35765515100"}, {"first_name"=>"Xinhui", "last_name"=>"Wang", "scopus_author_id"=>"53264965900"}, {"first_name"=>"Weiliang", "last_name"=>"Qui", "scopus_author_id"=>"56239284400"}, {"first_name"=>"Vincent", "last_name"=>"Carey", "scopus_author_id"=>"7006779984"}, {"first_name"=>"Wenche", "last_name"=>"Nystad", "scopus_author_id"=>"7004562667"}, {"first_name"=>"Siri E.", "last_name"=>"Håberg", "scopus_author_id"=>"20436043600"}, {"first_name"=>"Carole", "last_name"=>"Ober", "scopus_author_id"=>"7102639601"}, {"first_name"=>"Dan", "last_name"=>"Nicolae", "scopus_author_id"=>"6701908750"}, {"first_name"=>"Kathleen C.", "last_name"=>"Barnes", "scopus_author_id"=>"35394504000"}, {"first_name"=>"Fernando", "last_name"=>"Martinez", "scopus_author_id"=>"7402220268"}, {"first_name"=>"Andy", "last_name"=>"Liu", "scopus_author_id"=>"7402582215"}, {"first_name"=>"Robert", "last_name"=>"Lemanske", "scopus_author_id"=>"7006533736"}, {"first_name"=>"Robert", "last_name"=>"Strunk", "scopus_author_id"=>"7006404298"}, {"first_name"=>"Scott", "last_name"=>"Weiss", "scopus_author_id"=>"36040917900"}, {"first_name"=>"Stephanie", "last_name"=>"London", "scopus_author_id"=>"56988756100"}, {"first_name"=>"Frank", "last_name"=>"Gilliland", "scopus_author_id"=>"7007022537"}, {"first_name"=>"Benjamin", "last_name"=>"Raby", "scopus_author_id"=>"6603864707"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"373419069", "sgr"=>"84903535514", "issn"=>"19326203", "pmid"=>"24964093", "scopus"=>"2-s2.0-84903535514", "doi"=>"10.1371/journal.pone.0099716", "isbn"=>"1932-6203"}, "id"=>"d38c49e6-63c7-3128-a3df-835698c10948", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/prenatal-tobacco-smoke-exposure-associated-childhood-dna-cpg-methylation-3", "reader_count"=>50, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>4, "Researcher"=>17, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>7, "Student > Bachelor"=>2, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>4, "Researcher"=>17, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>7, "Student > Bachelor"=>2, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>8, "Agricultural and Biological Sciences"=>25, "Medicine and Dentistry"=>10, "Business, Management and Accounting"=>1, "Psychology"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>25}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>2}}, "reader_count_by_country"=>{"United States"=>1, "France"=>1, "Germany"=>2, "Spain"=>1}, "group_count"=>5}

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• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/dafc6432-8714-48a7-b91d-b8920bd51dd9", "title"=>"Epigenetics and the environment", "body"=>"I found the article by Breton et al (2014) to be fascinating. (1) Breton et al (2014) made an important step toward investigating a possible mechanism, epigenetic disruption, by which tobacco smoke could lead to chronic health problems. For years I have speculated about the possible role of epigenetic modifiers in the environment in influencing chronic disease risk. (2, 3, 4) It is good to see more investigations concerning this. This is a very important article on a very important topic, well-done Breton et al.\r\n\r\n\r\n\r\nReferences\r\n(1)\tBreton CV, et al. Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation. PLoS One. 2014 Jun 25;9(6):e99716.\r\n(2)\tRoss CM. Letter regarding article by Weitzman et al, \"tobacco smoke exposure is associated with the metabolic syndrome in adolescents\". Circulation. 2006 Mar 7;113(9):e393\r\n(3)\tRoss CM. Re: \"Cigarette smoking and incidence of first depressive episode: An 11-year, population-based follow-up study\". Am J Epidemiol. 2006 Nov 1;164(9):917-8.\r\n(4)\tRoss CM. A possible epigenetic explanation for the relationship between physical activity and exceptional health among older women. Arch Intern Med. 2010 Jun 28;170(12):1087.\r\n\r\n", "isRemoved"=>false, "created"=>"2014-07-25T10:46:24Z", "lastModified"=>"2014-07-25T10:46:24Z", "creator"=>{"userId"=>"61337"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pone.0099716", "state"=>"published", "journals"=>{"PLoSONE"=>{"journalKey"=>"PLoSONE", "eIssn"=>"1932-6203", "title"=>"PLOS ONE"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2014-07-25T10:46:24Z", "replies"=>[]}

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• {"files"=>["https://ndownloader.figshare.com/files/1565072"], "description"=>"<p>Boxplots showing the distribution of % CpG methylation after normalization and batch correction using COMBAT by IUS exposure for A) <i>C11orf52</i> (cg05697249), B) <i>XPNPEP1</i> (cg09352789), C) <i>FRMD4A</i> (cg25464840), and D) <i>PPEF2</i> (cg14724265) in 526 Asthma BRIDGE samples.</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "epidemiology", "Environmental epidemiology", "Genetic epidemiology", "Lifecourse epidemiology", "health care", "Environmental health", "Public and occupational health", "tobacco control", "Pulmonology", "asthma", "cpg", "methylation", "normalization", "batch", "correction", "ius", "526"], "article_id"=>1083304, "categories"=>["Biological Sciences"], "users"=>["Carrie V. Breton", "Kimberly D. Siegmund", "Bonnie R. Joubert", "Xinhui Wang", "Weiliang Qui", "Vincent Carey", "Wenche Nystad", "Siri E. Håberg", "Carole Ober", "Dan Nicolae", "Kathleen C. Barnes", "Fernando Martinez", "Andy Liu", "Robert Lemanske", "Robert Strunk", "Scott Weiss", "Stephanie London", "Frank Gilliland", "Benjamin Raby"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0099716.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Boxplots_showing_the_distribution_of_CpG_methylation_after_normalization_and_batch_correction_using_COMBAT_by_IUS_exposure_for_A_C11orf52_cg05697249_B_XPNPEP1_cg09352789_C_FRMD4A_cg25464840_and_D_PPEF2_cg14724265_in_526_Asthma_BRIDGE_samples_/1083304", "title"=>"Boxplots showing the distribution of % CpG methylation after normalization and batch correction using COMBAT by IUS exposure for A) <i>C11orf52</i> (cg05697249), B) <i>XPNPEP1</i> (cg09352789), C) <i>FRMD4A</i> (cg25464840), and D) <i>PPEF2</i> (cg14724265) in 526 Asthma BRIDGE samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-25 03:45:39"}
• {"files"=>["https://ndownloader.figshare.com/files/1565073"], "description"=>"<p>Descriptive characteristics of the CAMP study population (n = 527).</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "epidemiology", "Environmental epidemiology", "Genetic epidemiology", "Lifecourse epidemiology", "health care", "Environmental health", "Public and occupational health", "tobacco control", "Pulmonology", "asthma"], "article_id"=>1083305, "categories"=>["Biological Sciences"], "users"=>["Carrie V. Breton", "Kimberly D. Siegmund", "Bonnie R. Joubert", "Xinhui Wang", "Weiliang Qui", "Vincent Carey", "Wenche Nystad", "Siri E. Håberg", "Carole Ober", "Dan Nicolae", "Kathleen C. Barnes", "Fernando Martinez", "Andy Liu", "Robert Lemanske", "Robert Strunk", "Scott Weiss", "Stephanie London", "Frank Gilliland", "Benjamin Raby"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0099716.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Descriptive_characteristics_of_the_CAMP_study_population_n_8202_8202_527_/1083305", "title"=>"Descriptive characteristics of the CAMP study population (n = 527).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-25 03:45:39"}
• {"files"=>["https://ndownloader.figshare.com/files/1565075"], "description"=>"<p>CpG Loci significantly associated with IUS exposure in CAMP asthmatics (N = 527).</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "epidemiology", "Environmental epidemiology", "Genetic epidemiology", "Lifecourse epidemiology", "health care", "Environmental health", "Public and occupational health", "tobacco control", "Pulmonology", "asthma", "loci", "ius", "asthmatics"], "article_id"=>1083307, "categories"=>["Biological Sciences"], "users"=>["Carrie V. Breton", "Kimberly D. Siegmund", "Bonnie R. Joubert", "Xinhui Wang", "Weiliang Qui", "Vincent Carey", "Wenche Nystad", "Siri E. Håberg", "Carole Ober", "Dan Nicolae", "Kathleen C. Barnes", "Fernando Martinez", "Andy Liu", "Robert Lemanske", "Robert Strunk", "Scott Weiss", "Stephanie London", "Frank Gilliland", "Benjamin Raby"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0099716.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CpG_Loci_significantly_associated_with_IUS_exposure_in_CAMP_asthmatics_N_8202_8202_527_/1083307", "title"=>"CpG Loci significantly associated with IUS exposure in CAMP asthmatics (N = 527).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-25 03:45:39"}
• {"files"=>["https://ndownloader.figshare.com/files/1565076"], "description"=>"<p>Replication results from beta regression and linear regression models in Asthma BRIDGE and MoBa for the 19 CpG loci identified in CAMP.</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "epidemiology", "Environmental epidemiology", "Genetic epidemiology", "Lifecourse epidemiology", "health care", "Environmental health", "Public and occupational health", "tobacco control", "Pulmonology", "asthma", "beta", "regression", "linear", "moba", "19", "cpg", "loci"], "article_id"=>1083308, "categories"=>["Biological Sciences"], "users"=>["Carrie V. Breton", "Kimberly D. Siegmund", "Bonnie R. Joubert", "Xinhui Wang", "Weiliang Qui", "Vincent Carey", "Wenche Nystad", "Siri E. Håberg", "Carole Ober", "Dan Nicolae", "Kathleen C. Barnes", "Fernando Martinez", "Andy Liu", "Robert Lemanske", "Robert Strunk", "Scott Weiss", "Stephanie London", "Frank Gilliland", "Benjamin Raby"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0099716.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_results_from_beta_regression_and_linear_regression_models_in_Asthma_BRIDGE_and_MoBa_for_the_19_CpG_loci_identified_in_CAMP_/1083308", "title"=>"Replication results from beta regression and linear regression models in Asthma BRIDGE and MoBa for the 19 CpG loci identified in CAMP.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-25 03:45:39"}
• {"files"=>["https://ndownloader.figshare.com/files/2253880"], "description"=>"<div><p>Background</p><p>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.</p><p>Objectives</p><p>To characterize site-specific epigenetic modifications conferred by prenatal smoking exposure within asthmatic children.</p><p>Methods</p><p>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.</p><p>Results</p><p>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 <i>FRMD4A</i> (p = 0.01) and Cllorf52 (p = 0.001) compared to no exposure. Four additional genes, <i>XPNPEP1</i>, <i>PPEF2</i>, <i>SMPD3</i> and <i>CRYGN</i>, were nominally associated in at least one replication group.</p><p>Conclusions</p><p>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.</p></div>", "links"=>[], "tags"=>["Childhood DNA CpG Methylation BackgroundSmoking", "Asthma BRIDGE childhood asthmatics", "XPNPEP", "blood DNA samples", "Prenatal Tobacco Smoke Exposure", "smoke exposure", "SMPD", "PPEF", "quality control assessment", "asthmatic children.MethodsUsing Illumina HumanMethylation 27 microarrays", "fdr", "smoking exposure data", "methylation", "CRYGN", "4a", "Childhood Asthma Management Program", "replication group.ConclusionsThese data", "FRMD", "19 CpG loci"], "article_id"=>1536181, "categories"=>["Biological Sciences"], "users"=>["Carrie V. Breton", "Kimberly D. Siegmund", "Bonnie R. Joubert", "Xinhui Wang", "Weiliang Qui", "Vincent Carey", "Wenche Nystad", "Siri E. Håberg", "Carole Ober", "Dan Nicolae", "Kathleen C. Barnes", "Fernando Martinez", "Andy Liu", "Robert Lemanske", "Robert Strunk", "Scott Weiss", "Stephanie London", "Frank Gilliland", "Benjamin Raby"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0099716"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Prenatal_Tobacco_Smoke_Exposure_Is_Associated_with_Childhood_DNA_CpG_Methylation_/1536181", "title"=>"Prenatal Tobacco Smoke Exposure Is Associated with Childhood DNA CpG Methylation", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-25 13:06:13"}

PMC Usage Stats | Further Information

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• {"unique-ip"=>"16", "full-text"=>"10", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
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• {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
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• {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
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• {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
• {"unique-ip"=>"18", "full-text"=>"19", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
• {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
• {"unique-ip"=>"6", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
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• {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Anatomy", "average_usage"=>[267]}, {"subject_area"=>"/Biology and life sciences/Behavior", "average_usage"=>[333]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[282]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[306, 482]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[280]}, {"subject_area"=>"/Medicine and health sciences/Hematology", "average_usage"=>[256]}, {"subject_area"=>"/Medicine and health sciences/Pulmonology", "average_usage"=>[261, 417]}]}

F1000Prime