Genetic regulation of differentially methylated genes in visceral adipose tissue of severely obese men discordant for the metabolic syndrome
Abstract A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTLs) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. In order to pinpo...
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| container_title | Translational research : the journal of laboratory and clinical medicine |
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| creator | Guénard, Frédéric Tchernof, André Deshaies, Yves Biron, Simon Lescelleur, Odette Biertho, Laurent Marceau, Simon Pérusse, Louis Vohl, Marie-Claude |
| description | Abstract A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTLs) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. In order to pinpoint candidate genes for testing association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. Genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. Genome-wide association study conducted to identify SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations ( P |
| doi_str_mv | 10.1016/j.trsl.2017.01.002 |
| format | Article |
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The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. In order to pinpoint candidate genes for testing association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. Genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. Genome-wide association study conducted to identify SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations ( P <2.22x10-11 ) involving 2182 unique meQTL regulating methylation levels of 174 variable CpG sites. Two meQTLs disrupting CpG sites located within the collagen encoding COL11A2 gene were tested for associations with MetS and its components in a cohort of 3021 obese individuals. Rare allele of these meQTLs showed association with plasma fasting glucose levels. Further analysis conducted on these meQTL suggested a biological impact mediated through disruption of transcription factor (TF) binding sites based on prediction of TF binding affinities. The current study identified meQTL in VAT of severely obese men and revealed associations of two COL11A2 meQTL with fasting glucose levels.</description><identifier>ISSN: 1931-5244</identifier><identifier>EISSN: 1878-1810</identifier><identifier>DOI: 10.1016/j.trsl.2017.01.002</identifier><identifier>PMID: 28219716</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; CpG Islands ; DNA Methylation ; Epigenomics ; Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; Internal Medicine ; Intra-Abdominal Fat - pathology ; Intra-Abdominal Fat - physiology ; Male ; Metabolic Syndrome - genetics ; Middle Aged ; Obesity - genetics ; Obesity - pathology ; Obesity, Abdominal - genetics ; Obesity, Abdominal - pathology ; Polymorphism, Single Nucleotide</subject><ispartof>Translational research : the journal of laboratory and clinical medicine, 2017-06, Vol.184, p.1-11.e2</ispartof><rights>Elsevier Inc.</rights><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-24b7c8860cb285df8b24d35c6d8abfd5b2a815f5e3150e9961b940963fb6d8603</citedby><cites>FETCH-LOGICAL-c455t-24b7c8860cb285df8b24d35c6d8abfd5b2a815f5e3150e9961b940963fb6d8603</cites><orcidid>0000-0002-6242-4592</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.trsl.2017.01.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28219716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guénard, Frédéric</creatorcontrib><creatorcontrib>Tchernof, André</creatorcontrib><creatorcontrib>Deshaies, Yves</creatorcontrib><creatorcontrib>Biron, Simon</creatorcontrib><creatorcontrib>Lescelleur, Odette</creatorcontrib><creatorcontrib>Biertho, Laurent</creatorcontrib><creatorcontrib>Marceau, Simon</creatorcontrib><creatorcontrib>Pérusse, Louis</creatorcontrib><creatorcontrib>Vohl, Marie-Claude</creatorcontrib><title>Genetic regulation of differentially methylated genes in visceral adipose tissue of severely obese men discordant for the metabolic syndrome</title><title>Translational research : the journal of laboratory and clinical medicine</title><addtitle>Transl Res</addtitle><description>Abstract A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTLs) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. In order to pinpoint candidate genes for testing association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. Genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. Genome-wide association study conducted to identify SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations ( P <2.22x10-11 ) involving 2182 unique meQTL regulating methylation levels of 174 variable CpG sites. Two meQTLs disrupting CpG sites located within the collagen encoding COL11A2 gene were tested for associations with MetS and its components in a cohort of 3021 obese individuals. Rare allele of these meQTLs showed association with plasma fasting glucose levels. Further analysis conducted on these meQTL suggested a biological impact mediated through disruption of transcription factor (TF) binding sites based on prediction of TF binding affinities. The current study identified meQTL in VAT of severely obese men and revealed associations of two COL11A2 meQTL with fasting glucose levels.</description><subject>Adult</subject><subject>CpG Islands</subject><subject>DNA Methylation</subject><subject>Epigenomics</subject><subject>Gene Expression Regulation</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Intra-Abdominal Fat - pathology</subject><subject>Intra-Abdominal Fat - physiology</subject><subject>Male</subject><subject>Metabolic Syndrome - genetics</subject><subject>Middle Aged</subject><subject>Obesity - genetics</subject><subject>Obesity - pathology</subject><subject>Obesity, Abdominal - genetics</subject><subject>Obesity, Abdominal - pathology</subject><subject>Polymorphism, Single Nucleotide</subject><issn>1931-5244</issn><issn>1878-1810</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uk1rFTEUHUSxtfoHXEiWbuY1yWQyGRBBSq2FggsV3IV83GnzzCTPJPNg_oM_2gyvunDhKpfcc87lnnOb5jXBO4IJv9zvSsp-RzEZdpjsMKZPmnMiBtESQfDTWo8daXvK2FnzIuc9xoyPmD1vzqigZBwIP29-3UCA4gxKcL94VVwMKE7IummCBKE45f2KZigPa-2CRfcVn5EL6OiygaQ8UtYdYgZUXM4LbOwMx0quvKihNmYIVTCbmKwKBU0xofKwfRelo6-z8xpsijO8bJ5Nymd49fheNN8-Xn-9-tTefb65vfpw1xrW96WlTA9GCI6NpqK3k9CU2a433AqlJ9trqgTppx460mMYR070yPDIu0lXCMfdRfP2pHtI8ecCuch5W8Z7FSAuWVYPMWcDZxuUnqAmxZwTTPKQ3KzSKgmWWwpyL7cU5JaCxETWFCrpzaP-omewfyl_bK-AdycA1C2PDpLMxkEwYF0CU6SN7v_67_-hG--CM8r_gBXyPi4pVP8kkZlKLL9sd7CdQZ2MKRu-d78B6nyxIg</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Guénard, Frédéric</creator><creator>Tchernof, André</creator><creator>Deshaies, Yves</creator><creator>Biron, Simon</creator><creator>Lescelleur, Odette</creator><creator>Biertho, Laurent</creator><creator>Marceau, Simon</creator><creator>Pérusse, Louis</creator><creator>Vohl, Marie-Claude</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6242-4592</orcidid></search><sort><creationdate>20170601</creationdate><title>Genetic regulation of differentially methylated genes in visceral adipose tissue of severely obese men discordant for the metabolic syndrome</title><author>Guénard, Frédéric ; 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The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. In order to pinpoint candidate genes for testing association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. Genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites. Genome-wide association study conducted to identify SNPs (meQTL) associated with methylation levels at variable CpG sites revealed 2292 significant associations ( P <2.22x10-11 ) involving 2182 unique meQTL regulating methylation levels of 174 variable CpG sites. Two meQTLs disrupting CpG sites located within the collagen encoding COL11A2 gene were tested for associations with MetS and its components in a cohort of 3021 obese individuals. Rare allele of these meQTLs showed association with plasma fasting glucose levels. Further analysis conducted on these meQTL suggested a biological impact mediated through disruption of transcription factor (TF) binding sites based on prediction of TF binding affinities. The current study identified meQTL in VAT of severely obese men and revealed associations of two COL11A2 meQTL with fasting glucose levels.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28219716</pmid><doi>10.1016/j.trsl.2017.01.002</doi><orcidid>https://orcid.org/0000-0002-6242-4592</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult CpG Islands DNA Methylation Epigenomics Gene Expression Regulation Genome-Wide Association Study Humans Internal Medicine Intra-Abdominal Fat - pathology Intra-Abdominal Fat - physiology Male Metabolic Syndrome - genetics Middle Aged Obesity - genetics Obesity - pathology Obesity, Abdominal - genetics Obesity, Abdominal - pathology Polymorphism, Single Nucleotide |
| title | Genetic regulation of differentially methylated genes in visceral adipose tissue of severely obese men discordant for the metabolic syndrome |
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