Abstract 5010: Differences in DNA methylation between the African and European HapMap populations

Background: DNA methylation plays an important role in regulating gene transcription, and the genome-wide landscape of DNA methylation is altered in cancer: hypermethylation and silencing of tumor suppressor genes as well as hypomethylation of repetitive elements and target genes can contribute to cancer initiation and progression. As a complex trait itself, there is considerable inter-individual and inter-ethnic variability in DNA methylation patterns. To further explore the baseline variation of DNA methylation and its regulation, we have gathered genome-wide DNA methylation data on individual CpG methylation sites in a collection of human lymphoblastoid cell lines (LCLs) from the HapMap Project. Methods: We profiled DNA methylation in 73 unrelated African (YRI - Yoruba people from Ibadan, Nigeria) and 60 European ancestry (CEU - Caucasians from Utah, US) LCLs using the Illumina Human Methylation 450 BeadChip. This chip interrogates >485,000 CpG methylation sites per sample at single-nucleotide resolution and assigns each site an average beta value for methylation level. We controlled for potential batch effect due to array hybridization using COMBAT and removed probes that contained known SNPs or mapped ambiguously to the reference genome. In our final analysis dataset, we included 46,236 probes on autosomes that showed relatively high variation (top 25% percentile) across the LCL samples based on coefficient of variation. The Wilcox rank sum test was performed to identify differential methylation sites between the YRI and CEU samples. Results: In total, 988 CpG probes (708 genes) were found to be differentially methylated between these two populations (p −6 , false discovery rate −4 ). The differentially methylated sites were enriched in pathways and Gene Ontology terms such as “cell adhesion,” “ECM-receptor interaction,” and pathways involved in development such as WNT and Hedgehog. Conclusions: A substantial number of CpG methylation sites were differentially methylated between individuals of African and European ancestry. These differentially methylated CpG sites appeared to be enriched in certain genomic regions and pathways. Future integration of this dataset with other available resources of these samples (e.g., genotypes, mRNA expression) will help elucidate the complex networks of genetic and epigenetic regulation (e.g., through modified cytosine quantitative trait loci, mQTLs), and their contribution to complex traits, such as drug response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5010. doi:1538-7445.AM2012-5010