Schulz, Herbert, Ruppert, Ann-Kathrin, Herms, Stefan, Wolf, Christiane, Mirza-Schreiber, Nazanin, Stegle, Oliver, Czamara, Darina, Forstner, Andreas J, Sivalingam, Sugirthan, Schoch, Susanne et al (show 11 more authors)
(2017)
Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus.
NATURE COMMUNICATIONS, 8 (1).
1511-.
Text
Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus.pdf - Published version Download (1MB) |
Abstract
Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the cis-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify cis-meQTLs at 14,118 CpG methylation sites and cis-eQTLs for 302 3'-mRNA transcripts of 288 genes. Hippocampal cis-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. Cis-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of cis-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.
Item Type: | Article |
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Uncontrolled Keywords: | Hippocampus, Humans, Epilepsy, Temporal Lobe, Gene Expression Profiling, DNA Methylation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Adolescent, Adult, Aged, Middle Aged, Child, Child, Preschool, Infant, Female, Male, Genome-Wide Association Study, Young Adult |
Depositing User: | Symplectic Admin |
Date Deposited: | 04 Dec 2017 07:41 |
Last Modified: | 19 Jan 2023 06:48 |
DOI: | 10.1038/s41467-017-01818-4 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3013475 |