Identification of Genetic and Epigenetic Marks Involved in Population Structure

Abstract

Population structure is well known as a prevalent and important factor in genetic studies, but its relevance in epigenetics is unclear. Very little is known about the affected epigenetic markers and their connections with genetics. In this study we assessed the impact of population diversity on genome wide single nucleotide polymorphisms (SNPs) and DNA methylation levels in 196 participants from five ethnic groups, using principle and independent component analyses. Three population stratification factors (PSFs) were identified in the genomic SNP dataset, accounting for a relatively large portion of total variance (6%). In contrast, only one PSF was identified in genomic methylation dataset accounting for 0.2% of total variance. This methylation PSF, however, was significantly correlated with the largest SNP PSF (r = 0.72, p<1E-23). We then investigated the top contributing markers in these two linked PSFs. The SNP PSF predominantly consists of 8 SNPs from three genes, SLC45A2, HERC2 and CTNNA2, known to encode skin/hair/eye color. The methylation PSF includes 48 methylated sites in 44 genes coding for basic molecular functions, including transcription regulation, DNA binding, cytokine, and transferase activity. Among them, 8 sites are either hypo- or hyper-methylated correlating to minor alleles of SNPs in the SNP PSF. We found that the genes in SNP and methylation PSFs share common biological processes including sexual/multicellular organism reproduction, cell-cell signaling and cytoskeleton organization. We further investigated the transcription regulatory network operating at these genes and identified that most of genes closely interact with ID2, which encodes for a helix-loop-helix inhibitor of DNA binding. Overall, our results show a significant correlation between genetic and epigenetic population stratification, and suggest that the interrelationship between genetic and epigenetic population structure is mediated via complex multiple gene interactions in shared biological processes, through possibly, SNP-dependent modulation and ID2 repressor function.

Genetics of eye colours in different rural populations on the Silk Road

“…The most significant association was obtained with two SNPs, known as being strongly correlated with both blue and brown eye colours, located within HERC2 gene (rs1129038 and rs12913832; P-value ¼ 4.99 Â 10 À37 ). Other significant associations (P-valueo5 Â 10 À8 ) were found with both CTNNA2 (OMIM: 114025) 6 and OCA2 genes.…”

MB-COMTpromoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls

“…41 Furthermore, through principal and independent component analyses, Liu et al 41 found that the population structure present in DNA methylation data are very well captured by the first genetic principal component. Hence, to avoid confounding effects due to population stratification, we applied principal component analysis to our genotype data using EIGENSTRAT of the EIGENSOFT 3.0 software package, 42,43 and included the first principal component as covariate in our imaging models.…”

The epigenetic side of human adaptation: hypotheses, evidences and theories

“…A first one highlighted significant differences in global genomic DNA methylation of peripheral blood cells by ethnicity, suggesting that this individuals' information should be accurately considered in every methylation study (Zhang et al, 2011). The second one instead tried to assess the impact of population SNPs diversity patterns at the genome-wide level on DNA methylation profiles (Liu et al, 2010). For this purpose, around 200 samples of different self-reported ethnicity were analysed for 1M SNPs and for methylation status at 27 000 CpGs distributed across the whole genome.…”