Electronic Supplementary Material 4: Summary of genes associated to metal-DMR, gene location, reported interactions with BED effector proteins and associated ANN scores. from <i>In silico</i> epigenetics of metal exposure and subclinical atherosclerosis in middle age men: pilot results from the Aragon Workers Health Study Angela L. Riffo-Campos Azahara Fuentes-Trillo Wan Y. Tang Zoraida Soriano Griselda De Marco Pilar Rentero-Garrido Victoria Adam-Felici Veronica Lendinez-Tortajada Kevin Francesconi Walter Goessler Christine Ladd-Acosta Montse Leon-Latre Jose A. Casasnovas F. Javier Chaves Ana Navas-Acien Eliseo Guallar Maria Tellez-Plaza 10.6084/m9.figshare.5970235.v1 https://rs.figshare.com/articles/dataset/Electronic_Supplementary_Material_4_Summary_of_genes_associated_to_metal-DMR_gene_location_reported_interactions_with_BED_effector_proteins_and_associated_ANN_scores_from_i_In_silico_i_epigenetics_of_metal_exposure_and_subclinical_atherosclerosis_in_middl/5970235 We explored the association of metal levels with subclinical atherosclerosis and epigenetic changes in relevant biological pathways. Whole blood DNA Infinium Methylation 450 K data were obtained from 23 of 73 middle age men without clinically evident cardiovascular disease who participated in the Aragon Workers Health Study in 2009 (baseline visit) and had available baseline urinary metals and subclinical atherosclerosis measures obtained in 2010–2013 (follow-up visit). The median metal levels were 7.36 µg g<sup>−1</sup>, 0.33 µg g<sup>−1</sup>, 0.11 µg g<sup>−1</sup> and 0.07 µg g<sup>−1</sup>, for arsenic (sum of inorganic and methylated species), cadmium, antimony and tungsten, respectively. Urine cadmium and tungsten were associated with femoral and carotid intima-media thickness, respectively (Pearson's <i>r</i> = 0.27; <i>p</i> = 0.03 in both cases). Among nearest genes to identified differentially methylated regions (DMRs), 46% of metal-DMR genes overlapped with atherosclerosis-DMR genes (<i>p</i> < 0.001). Pathway enrichment analysis of atherosclerosis-DMR genes showed a role in inflammatory, metabolic and transport pathways. In <i>in silico</i> protein-to-protein interaction networks among proteins encoded by 162 and 108 genes attributed to atherosclerosis- and metal-DMRs, respectively, with proteins known to have a role in atherosclerosis pathways, we observed hub proteins in the network associated with both atherosclerosis and metal-DMRs (e.g. <i>SMAD3</i> and <i>NOP56</i>), and also hub proteins associated with metal-DMRs only but with relevant connections with atherosclerosis effectors (e.g. <i>SSTR5</i>, <i>HDAC4</i>, <i>AP2A2</i>, <i>CXCL12</i> and <i>SSTR4</i>). Our integrative <i>in silico</i> analysis demonstrates the feasibility of identifying epigenomic regions linked to environmental exposures and potentially involved in relevant pathways for human diseases. While our results support the hypothesis that metal exposures can influence health due to epigenetic changes, larger studies are needed to confirm our pilot results.This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’. 2018-03-10 05:14:46 environmental metals subclinical atherosclerosis DNA methylation cohort study