The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue.
Genetic variants that associate with DNA methylation at CpG sites (methylation quantitative trait loci, meQTLs) offer a potential biological mechanism of action for disease associated SNPs. We investigated whether meQTLs exist in abdominal subcutaneous adipose tissue (SAT) and if CpG methylation ass...
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oai:doaj.org-article:649fa27bf9c84420ad067f48835c3e702021-11-18T07:57:06ZThe presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue.1932-620310.1371/journal.pone.0055923https://doaj.org/article/649fa27bf9c84420ad067f48835c3e702013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23431366/?tool=EBIhttps://doaj.org/toc/1932-6203Genetic variants that associate with DNA methylation at CpG sites (methylation quantitative trait loci, meQTLs) offer a potential biological mechanism of action for disease associated SNPs. We investigated whether meQTLs exist in abdominal subcutaneous adipose tissue (SAT) and if CpG methylation associates with metabolic syndrome (MetSyn) phenotypes. We profiled 27,718 genomic regions in abdominal SAT samples of 38 unrelated individuals using differential methylation hybridization (DMH) together with genotypes at 5,227,243 SNPs and expression of 17,209 mRNA transcripts. Validation and replication of significant meQTLs was pursued in an independent cohort of 181 female twins. We find that, at 5% false discovery rate, methylation levels of 149 DMH regions associate with at least one SNP in a ±500 kilobase cis-region in our primary study. We sought to validate 19 of these in the replication study and find that five of these significantly associate with the corresponding meQTL SNPs from the primary study. We find that none of the 149 meQTL top SNPs is a significant expression quantitative trait locus in our expression data, but we observed association between expression levels of two mRNA transcripts and cis-methylation status. Our results indicate that DNA CpG methylation in abdominal SAT is partly under genetic control. This study provides a starting point for future investigations of DNA methylation in adipose tissue.Alexander W DrongGeorge NicholsonAsa K HedmanEshwar MeduriElin GrundbergKerrin S SmallSo-Youn ShinJordana T BellFredrik KarpeNicole SoranzoTim D SpectorMark I McCarthyPanos DeloukasMattias RantalainenCecilia M LindgrenMolPAGE ConsortiaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55923 (2013) |
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DOAJ |
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DOAJ |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Alexander W Drong George Nicholson Asa K Hedman Eshwar Meduri Elin Grundberg Kerrin S Small So-Youn Shin Jordana T Bell Fredrik Karpe Nicole Soranzo Tim D Spector Mark I McCarthy Panos Deloukas Mattias Rantalainen Cecilia M Lindgren MolPAGE Consortia The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue. |
| description |
Genetic variants that associate with DNA methylation at CpG sites (methylation quantitative trait loci, meQTLs) offer a potential biological mechanism of action for disease associated SNPs. We investigated whether meQTLs exist in abdominal subcutaneous adipose tissue (SAT) and if CpG methylation associates with metabolic syndrome (MetSyn) phenotypes. We profiled 27,718 genomic regions in abdominal SAT samples of 38 unrelated individuals using differential methylation hybridization (DMH) together with genotypes at 5,227,243 SNPs and expression of 17,209 mRNA transcripts. Validation and replication of significant meQTLs was pursued in an independent cohort of 181 female twins. We find that, at 5% false discovery rate, methylation levels of 149 DMH regions associate with at least one SNP in a ±500 kilobase cis-region in our primary study. We sought to validate 19 of these in the replication study and find that five of these significantly associate with the corresponding meQTL SNPs from the primary study. We find that none of the 149 meQTL top SNPs is a significant expression quantitative trait locus in our expression data, but we observed association between expression levels of two mRNA transcripts and cis-methylation status. Our results indicate that DNA CpG methylation in abdominal SAT is partly under genetic control. This study provides a starting point for future investigations of DNA methylation in adipose tissue. |
| format |
article |
| author |
Alexander W Drong George Nicholson Asa K Hedman Eshwar Meduri Elin Grundberg Kerrin S Small So-Youn Shin Jordana T Bell Fredrik Karpe Nicole Soranzo Tim D Spector Mark I McCarthy Panos Deloukas Mattias Rantalainen Cecilia M Lindgren MolPAGE Consortia |
| author_facet |
Alexander W Drong George Nicholson Asa K Hedman Eshwar Meduri Elin Grundberg Kerrin S Small So-Youn Shin Jordana T Bell Fredrik Karpe Nicole Soranzo Tim D Spector Mark I McCarthy Panos Deloukas Mattias Rantalainen Cecilia M Lindgren MolPAGE Consortia |
| author_sort |
Alexander W Drong |
| title |
The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue. |
| title_short |
The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue. |
| title_full |
The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue. |
| title_fullStr |
The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue. |
| title_full_unstemmed |
The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue. |
| title_sort |
presence of methylation quantitative trait loci indicates a direct genetic influence on the level of dna methylation in adipose tissue. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/649fa27bf9c84420ad067f48835c3e70 |
| work_keys_str_mv |
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1718422734630813696 |