The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue

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

Research output: Contribution to journalArticle (Academic Journal)peer-review

60 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)e55923
JournalPLoS ONE
Volume8
Issue number2
DOIs
Publication statusPublished - 2013

Keywords

  • Adult
  • Aged
  • Cohort Studies
  • CpG Islands
  • DNA Methylation
  • Female
  • Gene Frequency
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Metabolic Syndrome X
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • RNA, Messenger
  • Subcutaneous Fat, Abdominal
  • Transcriptome

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