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Table 1 Glossary of commonly used terms

From: Genetic impacts on DNA methylation: research findings and future perspectives

Term Definition
Additive genetic effects A genetic mechanism where alleles at one or more loci have a cumulative contribution to the phenotype. In human QTL analysis. An additive genetic model describes a model where the mean phenotype value changes by n units in heterozygotes and by 2n in homozygotes, with each additional copy of the risk allele at a locus. In heritability models, the contribution of additive genetic effects to the phenotype variance is estimated by the narrow-sense heritability.
Allele-specific methylation (ASM) Allelic asymmetry in DNA methylation status at a locus. ASM can be a consequence of several factors, such as genetic variation (sequence-dependent ASM, a type of meQTL effect) or genomic imprinting.
CpG island (CGI) Region of the genome where the frequency of CpG sites is greater than that expected by chance. Different definitions of CGI have been proposed. CGIs are flanked by regions known as CGI shores and shelves.
Differential methylation analysis Computational analysis that aims to identify a statistically significant difference in mean DNA methylation levels across sample groups. The approach can be applied to individual CpG sites (differentially methylated sites or positions, DMSs or DMPs) or to multiple consecutive CpG sites (differentially methylated region, DMR).
DNA methylation microarray Microarray-based technology that quantifies DNA methylation levels at a pre-specified set of CpG sites. Commonly used approaches typically apply bisulfite conversion of the DNA, followed by Illumina DNA methylation array profiling. Illumina methylation arrays include the Infinium HumanMethylation27 (27K), HumanMethylation450 (450K) and MethylationEPIC (EPIC) BeadChips. Different arrays profile different proportions of the methylome (coverage).
Epigenome-wide association study (EWAS) Analysis that systematically assesses the association between epigenetic marks (e.g., DNA methylation levels) at genetic loci across the genome and a phenotype or exposure of interest.
Genome-wide association study (GWAS) Analysis that systematically assesses the association between genetic variation at genetic loci across the genome and a phenotype of interest.
Heritability The proportion of variance in a phenotype that is attributed to the genetic variation. The broad-sense heritability describes the subset of phenotype variance due to all genetic effects, while the narrow-sense heritability describes the proportion of phenotype variance only due to additive genetic effects.
Methylation quantitative trait locus (meQTL) A genetic locus at which genetic variation is associated with variation in DNA methylation at a specific CpG site. MeQTLs can form local associations in cis, or have long-range effects in trans.
Methylome The DNA methylation profile of the genome. The methylome can be profiled at different levels of resolution, in single cells or in populations of cells, across different cells and tissues, and at a specific moment in time. It can be profiled using different technologies including WGBS and DNA methylation microarrays.
Multiple-testing correction When multiple simultaneous statistical tests are carried out, the probability of spurious discoveries increases. Different multiple testing correction procedures can be applied, including methods that control the false discovery rate (FDR) and the family-wise error rate (FWER), for example, Bonferroni correction.
Pleiotropy A genetic variant that impacts multiple phenotypes.
Post-GWAS analysis Follow-up analysis from GWAS that aims to characterize the functional role of GWAS signals and/or identify causal genetic variants. Many QTLs have been identified for variation in molecular processes, including but not limited to DNA methylation (meQTL), gene expression (eQTL) and histone modifications (hQTL).
QTL effect A quantitative measure that describes the strength and direction of association between a genetic variant and its associated phenotype, estimated in genetic association analysis.
Whole genome bisulfite sequencing (WGBS) Deep sequencing technology used to detect the methylation status of all sites in the methylome. WGBS consists of bisulfite conversion of the DNA, followed by whole genome sequencing.