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ARS Home » Northeast Area » Boston, Massachusetts » Research » Publications at this Location » Publication #307585
Title: SNPs located at CpG sites modulate genome-epigenome interaction

Author
item ZHI, DEGUI - University Of Alabama
item ASLIBEKYAN, STELLA - University Of Alabama
item IRVIN, M RYAN - University Of Alabama
item CLAAS, STEPHEN - University Of Alabama
item BORECKI, INGRID - University Of Alabama
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ABSHER, DEVAN - Hudsonalpha Institute For Biotechnology
item ARNETT, DONNA - University Of Alabama

Submitted to: Epigenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/21/2013
Publication Date: 8/1/2013
Citation: Zhi, D., Aslibekyan, S., Irvin, M., Claas, S.A., Borecki, I.B., Ordovas, J.M., Absher, D.M., Arnett, D.K. 2013. SNPs located at CpG sites modulate genome-epigenome interaction. Epigenetics. 8(8):802-806.

Interpretive Summary: DNA methylation is an important molecular-level process which alters the expression of genes in cells as they divide; that links genotypes, environmental factors and complex disease traits with how they are observably expressed. Previous studies have found local correlation between genetic variants and DNA methylation levels. However, the mechanisms underlying these relationships are unclear. We investigated these mechanisms using DNA methylation data from participants on the Genetics of Lipid Lowering Drugs and Diet Network study participants (n = 593). We found that over 80% of genetic variants at specific DNA sites called CpG are known to be capable of turning ‘off’ a genes associated with DNA methylation levels. Beyond direct effects on the methylation, these variants were associated with lowered methylation of CpG sites located within 45 base pairs. The effect of these variants extends to as far as 10 kilobase pairs and can contribute to the observed DNA methylation level signals in the surrounding region. In conclusion, these variants at CpG sites are responsible for a large portion of observed DNA methylation levels in the human genome and play a crucial role in the biological process linking genetic variation, with epigenetic changes and environmental and behavioral factors, such as dietary habits.

Technical Abstract: DNA methylation is an important molecular-level phenotype that links genotypes and complex disease traits. Previous studies have found local correlation between genetic variants and DNA methylation levels (cis-meQTLs). However, general mechanisms underlying cis-meQTLs are unclear. We conducted a cis-meQTL analysis of the Genetics of Lipid Lowering Drugs and Diet Network data (n = 593). We found that over 80% of genetic variants at CpG sites (meSNPs) are meQTL loci (P-value<10**-9), and meSNPs account for over two thirds of the strongest meQTL signals (P-value<10**-200). Beyond direct effects on the methylation of the meSNP site, the CpG-disrupting allele of meSNPs were associated with lowered methylation of CpG sites located within 45 bp. The effect of meSNPs extends to as far as 10 kb and can contribute to the observed meQTL signals in the surrounding region, likely through correlated methylation patterns and linkage disequilibrium. Therefore, meSNPs are behind a large portion of observed meQTL signals and play a crucial role in the biological process linking genetic variation to epigenetic changes.