Quantitative studies of DNA methylation and gene expression in neuropsychiatric traits

摘要: Research has shown that besides genes and environment, epigenetic factors are also playing a role in the development of traits diseases. Epigenetic changes do not affect underlying DNA sequence, but its structure is thought to play major regulation gene expression. methylation, one most-characterized mechanisms, involves attachment methyl group cytosine cytosine-phosphate-guanine (CpG) pair. CpG sites often cluster promoter regions genes, which important for control We hypothesize differences methylation involved disease susceptibility including schizophrenia. Schizophrenia neuropsychiatric disorder affecting ~1% population. The characterized by positive symptoms (e.g. hallucinations, delusions), negative social withdrawal poverty speech). Despite high heritability estimate roughly 80%, only small proportion can be explained currently known loci. In this thesis, we aimed study different layers genomic data (genetic variation, expression) simultaneously order get more insight into biological mechanisms First, studied association between expression, genetic variation whole blood healthy controls. observed complex variable patterns Secondly, used results from large schizophrenia genome-wide select loci differential expression cases versus identified three under disease-associated alleles observe levels our third study, combined with profiles. confirmed single nucleotide polymorphisms (SNPs), regulate differentially methylated schizophrenia, enriched alleles. were able provide specific molecular mechanism at least locus. examined using 22 nuclear families. extensive interaction levels, includes identification ‘variation SNPs’ so much median level rather variance levels. Since brain disorder, samples patients subjects. One most significant linked micro-RNA137 (miRNA-137). miRNAs non-coding RNA molecules key players Using these samples, relation miRNA-137 methylation. Our findings suggest possible link miRNA serotonergic glutamatergic pathways. To conclude, described methods combine analyse types information. Integrating genotype led possibly contribute