• Suhre, Karsten
• Al-Shafai, Mashael
• Muftah, Wadha A. Al
• Zaghlool, Shaza B.
• Falchi, Mario
• Kumar, Pankaj

Abstract

Background:<p class="Para">Modification of DNA bymethylation of cytosines at CpG dinucleotides is a widespread phenomenonthat leads to changes in gene expression, thereby influencing andregulating many biological processes. Recent technical advances in thegenome-wide determination of single-base DNA-methylation enabledepigenome-wide association studies (EWASs). Early EWASs establishedrobust associations between age and gender with the degree of CpGmethylation at specific sites. Other studies uncovered associations withcigarette smoking. However, so far these studies were mainly conductedin Caucasians, raising the question of whether these findings can alsobe extrapolated to other populations.</p>Results:<p class="Para">Here, we present an EWAS withage, gender, and smoking status in a family study of 123 individuals ofArab descent. We determined DNA methylation at over 450,000 CpG sitesusing the Illumina Infinium HumanMethylation450 BeadChip, appliedstate-of-the-art data processing protocols, including correction forblood cell type heterogeneity and hidden confounders, and eliminatedprobes containing SNPs at the targeted CpG site using 40× whole-genomesequencing data. Using this approach, we could replicate the leadingpublished EWAS associations with age, gender and smoking, and recoveredhallmarks of gender-specific epigenetic changes. Interestingly, we couldeven replicate the recently reported precise prediction ofchronological age based on the methylation of only a few selected CpGsites.</p>Conclusion:<p class="Para">Our study supports the viewthat when applied with state-of-the art protocols to account for allpotential confounders, DNA methylation arrays represent powerful toolsfor EWAS with more complex phenotypes that can also be successfullyapplied to non-Caucasian populations.</p>

Topics

• impedance spectroscopy