title: Association of DNA methylation with age, gender, and smoking in an Arab population.
abstract: BACKGROUND
  Modification of DNA by methylation of cytosines at CpG dinucleotides is a widespread phenomenon that leads to changes in gene expression, thereby influencing and regulating many biological processes. Recent technical advances in the genome-wide determination of single-base DNA-methylation enabled epigenome-wide association studies (EWASs). Early EWASs established robust associations between age and gender with the degree of CpG methylation at specific sites. Other studies uncovered associations with cigarette smoking. However, so far these studies were mainly conducted in Caucasians, raising the question of whether these findings can also be extrapolated to other populations.
  
  
  RESULTS
  Here, we present an EWAS with age, gender, and smoking status in a family study of 123 individuals of Arab descent. We determined DNA methylation at over 450,000 CpG sites using the Illumina Infinium HumanMethylation450 BeadChip, applied state-of-the-art data processing protocols, including correction for blood cell type heterogeneity and hidden confounders, and eliminated probes containing SNPs at the targeted CpG site using 40× whole-genome sequencing data. Using this approach, we could replicate the leading published EWAS associations with age, gender and smoking, and recovered hallmarks of gender-specific epigenetic changes. Interestingly, we could even replicate the recently reported precise prediction of chronological age based on the methylation of only a few selected CpG sites.
  
  
  CONCLUSIONS
  Our study supports the view that when applied with state-of-the art protocols to account for all potential confounders, DNA methylation arrays represent powerful tools for EWAS with more complex phenotypes that can also be successfully applied to non-Caucasian populations.
authors: Bioinformatics Core, Weill Cornell Medical College in Qatar, Education City, PO Box 24144, Doha, Qatar ; Computer Engineering Department, Virginia Tech, Blacksburg, VA 24060 USA.
authors: Shaza B
authors: SB
authors: Zaghlool
authors: Bioinformatics Core, Weill Cornell Medical College in Qatar, Education City, PO Box 24144, Doha, Qatar ; Department of Genomics of Common Disease, Imperial College London, London, UK ; Research Division, Qatar Science Leadership Program, Qatar Foundation, Doha, Qatar.
authors: Mashael
authors: M
authors: Al-Shafai
authors: Bioinformatics Core, Weill Cornell Medical College in Qatar, Education City, PO Box 24144, Doha, Qatar ; Department of Genomics of Common Disease, Imperial College London, London, UK ; Research Division, Qatar Science Leadership Program, Qatar Foundation, Doha, Qatar.
authors: Wadha A
authors: WA
authors: Al Muftah
authors: Bioinformatics Core, Weill Cornell Medical College in Qatar, Education City, PO Box 24144, Doha, Qatar.
authors: Pankaj
authors: P
authors: Kumar
authors: Department of Genomics of Common Disease, Imperial College London, London, UK.
authors: Mario
authors: M
authors: Falchi
authors: Bioinformatics Core, Weill Cornell Medical College in Qatar, Education City, PO Box 24144, Doha, Qatar ; Helmholtz Zentrum München, Germany, Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors: Karsten
authors: K
authors: Suhre
keywords: Age; Association study; DNA methylation; Epigenetics; Gender; Smoking