Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type

Alicia K. Smith, Varun Kilaru, Mehmet Kocak, Lynn M. Almli, Kristina B. Mercer, Kerry J. Ressler, Frances Tylavsky, Karen N. Conneely

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number145
JournalBMC Genomics
Volume15
Issue number1
DOIs
StatePublished - Feb 21 2014

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Quantitative Trait Loci
Methylation
Single Nucleotide Polymorphism
DNA Methylation
Linear Models
Genotype
Physiological Phenomena
Gene-Environment Interaction
Brain
MicroRNAs
Bipolar Disorder
African Americans
Binding Sites
Newborn Infant
Genome
Population
Genes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Genetics

Cite this

Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. / Smith, Alicia K.; Kilaru, Varun; Kocak, Mehmet; Almli, Lynn M.; Mercer, Kristina B.; Ressler, Kerry J.; Tylavsky, Frances; Conneely, Karen N.

In: BMC Genomics, Vol. 15, No. 1, 145, 21.02.2014.

Research output: Contribution to journalArticle

Smith, Alicia K. ; Kilaru, Varun ; Kocak, Mehmet ; Almli, Lynn M. ; Mercer, Kristina B. ; Ressler, Kerry J. ; Tylavsky, Frances ; Conneely, Karen N. / Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. In: BMC Genomics. 2014 ; Vol. 15, No. 1.
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