Fetal DNA Methylation Associates with Early Spontaneous Preterm Birth and Gestational Age
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{"title"=>"Fetal DNA Methylation Associates with Early Spontaneous Preterm Birth and Gestational Age", "type"=>"journal", "authors"=>[{"first_name"=>"Sasha E.", "last_name"=>"Parets", "scopus_author_id"=>"56049572100"}, {"first_name"=>"Karen N.", "last_name"=>"Conneely", "scopus_author_id"=>"9334492400"}, {"first_name"=>"Varun", "last_name"=>"Kilaru", "scopus_author_id"=>"40761783000"}, {"first_name"=>"Stephen J.", "last_name"=>"Fortunato", "scopus_author_id"=>"7005680831"}, {"first_name"=>"Tariq Ali", "last_name"=>"Syed", "scopus_author_id"=>"55509921000"}, {"first_name"=>"George", "last_name"=>"Saade", "scopus_author_id"=>"7006942866"}, {"first_name"=>"Alicia K.", "last_name"=>"Smith", "scopus_author_id"=>"37102606600"}, {"first_name"=>"Ramkumar", "last_name"=>"Menon", "scopus_author_id"=>"35566257700"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84879541829", "doi"=>"10.1371/journal.pone.0067489", "pui"=>"369208926", "pmid"=>"23826308", "scopus"=>"2-s2.0-84879541829", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"e1b15ac1-5351-3c25-ac25-a306ebb0df92", "abstract"=>"Spontaneous preterm birth (PTB, <37 weeks gestation) is a major public health concern, and children born preterm have a higher risk of morbidity and mortality throughout their lives. Recent studies suggest that fetal DNA methylation of several genes varies across a range of gestational ages (GA), but it is not yet clear if fetal epigenetic changes associate with PTB. The objective of this study is to interrogate methylation patterns across the genome in fetal leukocyte DNA from African Americans with early PTB (24(1/7)-34(0/7) weeks; N = 22) or term births (39(0/7)-40(6/7)weeks; N = 28) and to evaluate the association of each CpG site with PTB and GA. DNA methylation was assessed across the genome with the HumanMethylation450 BeadChip. For each individual sample and CpG site, the proportion of DNA methylation was estimated. The associations between methylation and PTB or GA were evaluated by fitting a separate linear model for each CpG site, adjusting for relevant covariates. Overall, 29 CpG sites associated with PTB (FDR<.05; 5.7×10(-10)<p<2.9×10(-6)) independent of GA. Also, 9637 sites associated with GA (FDR<.05; 9.5×10(-16)<p<1.0×10(-3)), with 61.8% decreasing in methylation with shorter GA. GA-associated CpG sites were depleted in the CpG islands of their respective genes (p<2.2×10(-16)). Gene set enrichment analysis (GSEA) supported enrichment of GA-associated CpG sites in genes that play a role in embryonic development as well as the extracellular matrix. Additionally, this study replicated the association of several CpG sites associated with gestational age in other studies (CRHBP, PIK3CD and AVP). Dramatic differences in fetal DNA methylation are evident in fetuses born preterm versus at term, and the patterns established at birth may provide insight into the long-term consequences associated with PTB.", "link"=>"http://www.mendeley.com/research/fetal-dna-methylation-associates-early-spontaneous-preterm-birth-gestational-age", "reader_count"=>46, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>4, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>4, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>8, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>11, "Psychology"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Uruguay"=>2, "United States"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1103063"], "description"=>"<p>All subjects are African American.</p>*<p>NS indicates the p-value is not significant (p>.05).</p>", "links"=>[], "tags"=>["Obstetrics and gynecology", "Labor and delivery", "pregnancy"], "article_id"=>733088, "categories"=>["Medicine"], "users"=>["Sasha E. Parets", "Karen N. Conneely", "Varun Kilaru", "Stephen J. Fortunato", "Tariq Ali Syed", "George Saade", "Alicia K. Smith", "Ramkumar Menon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067489.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_and_demographic_characteristics_of_the_cohort_/733088", "title"=>"Clinical and demographic characteristics of the cohort.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-27 02:14:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1103061"], "description"=>"<p>Δβ represents the average methylation difference between early PTB and term birth after adjustment for covariates.</p>", "links"=>[], "tags"=>["Obstetrics and gynecology", "Labor and delivery", "pregnancy", "cpg", "sites", "ptb"], "article_id"=>733086, "categories"=>["Medicine"], "users"=>["Sasha E. Parets", "Karen N. Conneely", "Varun Kilaru", "Stephen J. Fortunato", "Tariq Ali Syed", "George Saade", "Alicia K. Smith", "Ramkumar Menon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067489.t002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_29_CpG_sites_that_associated_with_PTB_adjusted_for_GA_/733086", "title"=>"29 CpG sites that associated with PTB (adjusted for GA).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-27 02:14:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1103066", "https://ndownloader.figshare.com/files/1103067", "https://ndownloader.figshare.com/files/1103068"], "description"=>"<div><p>Spontaneous preterm birth (PTB, <37 weeks gestation) is a major public health concern, and children born preterm have a higher risk of morbidity and mortality throughout their lives. Recent studies suggest that fetal DNA methylation of several genes varies across a range of gestational ages (GA), but it is not yet clear if fetal epigenetic changes associate with PTB. The objective of this study is to interrogate methylation patterns across the genome in fetal leukocyte DNA from African Americans with early PTB (24<sup>1/7</sup>–34<sup>0/7</sup> weeks; N = 22) or term births (39<sup>0/7</sup>–40<sup>6/7</sup>weeks; N = 28) and to evaluate the association of each CpG site with PTB and GA. DNA methylation was assessed across the genome with the HumanMethylation450 BeadChip. For each individual sample and CpG site, the proportion of DNA methylation was estimated. The associations between methylation and PTB or GA were evaluated by fitting a separate linear model for each CpG site, adjusting for relevant covariates. Overall, 29 CpG sites associated with PTB (FDR<.05; 5.7×10<sup>−10</sup>−6) independent of GA. Also, 9637 sites associated with GA (FDR<.05; 9.5×10<sup>−16</sup>−3), with 61.8% decreasing in methylation with shorter GA. GA-associated CpG sites were depleted in the CpG islands of their respective genes (p<2.2×10<sup>−16</sup>). Gene set enrichment analysis (GSEA) supported enrichment of GA-associated CpG sites in genes that play a role in embryonic development as well as the extracellular matrix. Additionally, this study replicated the association of several CpG sites associated with gestational age in other studies (<i>CRHBP</i>, <i>PIK3CD</i> and <i>AVP</i>). Dramatic differences in fetal DNA methylation are evident in fetuses born preterm versus at term, and the patterns established at birth may provide insight into the long-term consequences associated with PTB.</p></div>", "links"=>[], "tags"=>["Obstetrics and gynecology", "Labor and delivery", "pregnancy", "dna", "methylation", "associates", "spontaneous", "preterm", "gestational"], "article_id"=>733091, "categories"=>["Medicine"], "users"=>["Sasha E. Parets", "Karen N. Conneely", "Varun Kilaru", "Stephen J. Fortunato", "Tariq Ali Syed", "George Saade", "Alicia K. Smith", "Ramkumar Menon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0067489.s001", "https://dx.doi.org/10.1371/journal.pone.0067489.s002", "https://dx.doi.org/10.1371/journal.pone.0067489.s003"], "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fetal_DNA_Methylation_Associates_with_Early_Spontaneous_Preterm_Birth_and_Gestational_Age_/733091", "title"=>"Fetal DNA Methylation Associates with Early Spontaneous Preterm Birth and Gestational Age", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-06-27 02:14:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1103065"], "description"=>"<p>Δβ per week represents the average increase in β-value associated with each additional week of GA.</p>", "links"=>[], "tags"=>["Obstetrics and gynecology", "Labor and delivery", "pregnancy", "cpg", "sites", "ga"], "article_id"=>733090, "categories"=>["Medicine"], "users"=>["Sasha E. Parets", "Karen N. Conneely", "Varun Kilaru", "Stephen J. Fortunato", "Tariq Ali Syed", "George Saade", "Alicia K. Smith", "Ramkumar Menon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067489.t005", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_of_CpG_sites_previously_associated_with_GA_18_/733090", "title"=>"Replication of CpG sites previously associated with GA [18].", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-27 02:14:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1103060"], "description"=>"<p>The y-axis is the negative log10 of the p-value for the association while the x-axis is position on each chromosome. The dashed line indicates experiment-wide significance. Genomic locations of each CpG site are in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067489#pone.0067489.s003\" target=\"_blank\">Table S1</a>.</p>", "links"=>[], "tags"=>["Obstetrics and gynecology", "Labor and delivery", "pregnancy", "depicting", "cpg", "sites", "ptb"], "article_id"=>733085, "categories"=>["Medicine"], "users"=>["Sasha E. Parets", "Karen N. Conneely", "Varun Kilaru", "Stephen J. Fortunato", "Tariq Ali Syed", "George Saade", "Alicia K. Smith", "Ramkumar Menon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067489.g001", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Manhattan_plots_depicting_the_association_of_all_CpG_sites_with_A_PTB_and_with_B_GA_/733085", "title"=>"Manhattan plots depicting the association of all CpG sites with (A) PTB and with (B) GA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-27 02:14:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1103064"], "description"=>"<p>NES is the normalized enrichment score.</p>", "links"=>[], "tags"=>["Obstetrics and gynecology", "Labor and delivery", "pregnancy", "enrichment", "cpg", "sites", "ga"], "article_id"=>733089, "categories"=>["Medicine"], "users"=>["Sasha E. Parets", "Karen N. Conneely", "Varun Kilaru", "Stephen J. Fortunato", "Tariq Ali Syed", "George Saade", "Alicia K. Smith", "Ramkumar Menon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067489.t004", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_enrichment_analysis_of_CpG_sites_that_associated_with_GA_FDR_lt_05_/733089", "title"=>"Gene enrichment analysis of CpG sites that associated with GA (FDR<.05).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-27 02:14:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1103062"], "description"=>"<p>Note that each row in the table represents a Fisher’s exact test that tests for enrichment of associated or unassociated sites for the relevant category (e.g. CpG islands).</p>*<p>NS indicates the p-value is not significant (p>.05).</p>", "links"=>[], "tags"=>["Obstetrics and gynecology", "Labor and delivery", "pregnancy", "enrichment", "regions", "t-statistic", "cpg"], "article_id"=>733087, "categories"=>["Medicine"], "users"=>["Sasha E. Parets", "Karen N. Conneely", "Varun Kilaru", "Stephen J. Fortunato", "Tariq Ali Syed", "George Saade", "Alicia K. Smith", "Ramkumar Menon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067489.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Enrichment_analysis_to_examine_whether_there_is_a_an_enrichment_in_certain_regions_that_associated_with_GA_or_whether_there_is_an_enrichment_of_a_certain_direction_of_a_t_statistic_for_associated_CpG_sites_/733087", "title"=>"Enrichment analysis to examine whether there is a an enrichment in certain regions that associated with GA, or whether there is an enrichment of a certain direction of a t-statistic for associated CpG sites.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-27 02:14:21"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"69", "full-text"=>"73", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
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Relative Metric

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