Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus.
Herbert SchulzAnn-Kathrin RuppertStefan HermsChristiane WolfNazanin Mirza-SchreiberOliver StegleDarina CzamaraAndreas J ForstnerSugirthan SivalingamSusanne SchochSusanne MoebusBenno PützAxel HillmerNadine FrickerHartmut VatterBertram Müller-MyhsokMarkus M NöthenAlbert J BeckerPer HoffmannThomas SanderSven CichonPublished in: Nature communications (2017)
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.
Keyphrases
- genome wide
- dna methylation
- gene expression
- cerebral ischemia
- transcription factor
- copy number
- endothelial cells
- resting state
- subarachnoid hemorrhage
- white matter
- brain injury
- blood brain barrier
- high resolution
- poor prognosis
- bipolar disorder
- temporal lobe epilepsy
- functional connectivity
- binding protein
- induced pluripotent stem cells
- dna binding
- high density
- single molecule
- congenital heart disease