Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus


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-.

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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
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
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