title: Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type.
abstract: BACKGROUND
  Individual genotypes at specific loci can result in different patterns of DNA methylation. These methylation quantitative trait loci (meQTLs) influence methylation across extended genomic regions and may underlie direct SNP associations or gene-environment interactions. We hypothesized that the detection of meQTLs varies with ancestral population, developmental stage, and tissue type. We explored this by analyzing seven datasets that varied by ancestry (African American vs. Caucasian), developmental stage (neonate vs. adult), and tissue type (blood vs. four regions of postmortem brain) with genome-wide DNA methylation and SNP data. We tested for meQTLs by constructing linear regression models of methylation levels at each CpG site on SNP genotypes within 50 kb under an additive model controlling for multiple tests.
  
  
  RESULTS
  Most meQTLs mapped to intronic regions, although a limited number appeared to occur in synonymous or nonsynonymous coding SNPs. We saw significant overlap of meQTLs between ancestral groups, developmental stages, and tissue types, with the highest rates of overlap within the four brain regions. Compared with a random group of SNPs with comparable frequencies, meQTLs were more likely to be 1) represented among the most associated SNPs in the WTCCC bipolar disorder results and 2) located in microRNA binding sites.
  
  
  CONCLUSIONS
  These data give us insight into how SNPs impact gene regulation and support the notion that peripheral blood may be a reliable correlate of physiological processes in other tissues.
authors.affiliation: Department of Psychiatry and Behavioral Science, Emory University, 101 Woodruff Circle NE; Ste 4000, Atlanta, GA 30322, USA. alicia.smith@emory.edu.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Smith
authors.forename: Varun
authors.initials: V
authors.lastname: Kilaru
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Almli
authors.forename: Kristina B
authors.initials: KB
authors.lastname: Mercer
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.forename: Frances A
authors.initials: FA
authors.lastname: Tylavsky
authors.forename: Karen N
authors.initials: KN
authors.lastname: Conneely
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D005260:Female; D005786:Gene Expression Regulation; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci