Genetic-epigenetic interactions in cis: a major focus in the post-GWAS era

• Published in: Genome Biology Vol. 18; no. 1; p. 120
• Main Authors: Do, Catherine, Shearer, Alyssa, Suzuki, Masako, Terry, Mary Beth, Gelernter, Joel, Greally, John M, Tycko, Benjamin
• Format: Journal Article
• Language: English
• Published: England BioMed Central 19.06.2017; BMC
• Subjects: Alleles; Binding sites; Bioinformatics; Brain; Consortia; CpG Islands - genetics; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; Epigenesis, Genetic; Epigenetics; Gene mapping; Genome-wide association studies; Genome-Wide Association Study; Genomes; Haplotypes; Haplotypes - genetics; Humans; Mental disorders; Nucleotide sequence; Placenta; Polymorphism, Single Nucleotide - genetics; Quantitative trait loci; Quantitative Trait Loci - genetics; Regulatory sequences; Review; Transcription factors
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-017-1250-y

Studies on genetic-epigenetic interactions, including the mapping of methylation quantitative trait loci (mQTLs) and haplotype-dependent allele-specific DNA methylation (hap-ASM), have become a major focus in the post-genome-wide-association-study (GWAS) era. Such maps can nominate regulatory sequence variants that underlie GWAS signals for common diseases, ranging from neuropsychiatric disorders to cancers. Conversely, mQTLs need to be filtered out when searching for non-genetic effects in epigenome-wide association studies (EWAS). Sequence variants in CCCTC-binding factor (CTCF) and transcription factor binding sites have been mechanistically linked to mQTLs and hap-ASM. Identifying these sites can point to disease-associated transcriptional pathways, with implications for targeted treatment and prevention.