Complex Disease Epigenetics Group

Leveraging the power of long-read RNA sequencing, a new paper from our group published in Cell Reports has identified thousands of novel transcripts in the human and mouse cortex. These novel transcripts, not present in existing genome annotations, were characterised with novel splicing events and splice junctions. We further observed differential transcript usage between human fetal and adult cortex, confirming the importance of alterna...

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This theme supports generating various diagrams from a text description using jekyll-diagrams plugin. Below, we generate a few examples of such diagrams using languages such as mermaid, plantuml, vega-lite, etc.

Note:

Equations

This theme supports rendering beautiful math in inline and display modes using MathJax 3 engine. You just need to surround your math expression with $$, like $$ E = mc^2 $$. If you leave it inside a paragraph, it will produce an inline expression, just like \(E = mc^2\).

To use display mode, again ...

A sample blog page that demonstrates the accessing of github meta data.

What does Github-MetaData do?

• Propagates the site.github namespace with repository metadata
• Setting site variables :
  • site.title
  • site.description
  • site.url
  • site.baseurl
• Accessing the metadata - duh.
• Generating edittable links.

Tweets by PsyEpigenetics

selected publications

1. Functional characterization of the schizophrenia associated gene AS3MT identifies a role in neuronal development

   Sam J. Washer, Robert Flynn, Asami Oguro-Ando, and 5 more authors

   AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, Jul 2022

   Abs

   Genome-wide association studies (GWAS) have identified multiple genomic regions associated with schizophrenia, although many variants reside in noncoding regions characterized by high linkage disequilibrium (LD) making the elucidation of molecular mechanisms challenging. A genomic region on chromosome 10q24 has been consistently associated with schizophrenia with risk attributed to the AS3MT gene. Although AS3MT is hypothesized to play a role in neuronal development and differentiation, work to fully understand the function of this gene has been limited. In this study we explored the function of AS3MT using a neuronal cell line (SH-SY5Y). We confirm previous findings of isoform specific expression of AS3MT during SH-SY5Y differentiation toward neuronal fates. Using CRISPR-Cas9 gene editing we generated AS3MT knockout SH-SY5Y cell lines and used RNA-seq to identify significant changes in gene expression in pathways associated with neuronal development, inflammation, extracellular matrix formation, and RNA processing, including dysregulation of other genes strongly implicated in schizophrenia. We did not observe any morphological changes in cell size and neurite length following neuronal differentiation and MAP2 immunocytochemistry. These results provide novel insights into the potential role of AS3MT in brain development and identify pathways through which genetic variation in this region may confer risk for schizophrenia.

2. Characterizing genetic and environmental influences on variable DNA methylation using monozygotic and dizygotic twins

   Eilis Hannon, Olivia Knox, Karen Sugden, and 8 more authors

   PLOS GENETICS, Aug 2018

   Abs

   Variation in DNA methylation is being increasingly associated with health and disease outcomes. Although DNA methylation is hypothesized to be a mechanism by which both genetic and non-genetic factors can influence the regulation of gene expression, little is known about the extent to which DNA methylation at specific sites is influenced by heritable as well as environmental factors. We quantified DNA methylation in whole blood at age 18 in a birth cohort of 1,464 individuals comprising 426 monozygotic (MZ) and 306 same-sex dizygotic (DZ) twin pairs. Site-specific levels of DNA methylation were more strongly correlated across the genome between MZ than DZ twins. Structural equation models revealed that although the average contribution of additive genetic influences on DNA methylation across the genome was relatively low, it was notably elevated at the highly variable sites characterized by intermediate levels of DNAm that are most relevant for epigenetic epidemiology. Sites at which variable DNA methylation was most influenced by genetic factors were significantly enriched for DNA methylation quantitative trait loci (mQTL) effects, and overlapped with sites where inter-individual variation correlates across tissues. Finally, we show that DNA methylation at sites robustly associated with environmental exposures such as tobacco smoking and obesity is also influenced by additive genetic effects, highlighting the need to control for genetic background in analyses of exposure-associated DNA methylation differences. Estimates of the contribution of genetic and environmental influences to DNA methylation at all sites profiled in this study are available as a resource for the research community (http://www.epigenomicslab.com/online-data-resources).

3. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

   Naomi R. Wray, Stephan Ripke, Manuel Mattheisen, and 215 more authors

   NATURE GENETICS, May 2018

   Abs

   Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.