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VCU researchers receive $2.1 million grant to investigate genetic markers for schizophrenia

March 2017: The National Institute of Mental Health has awarded a $2.1 million grant to Virginia Commonwealth University’s Center for Biomarker Research and Precision Medicine to study potential epigenetic causes of schizophrenia.

The purpose of the four-year grant is to study DNA methylation as it relates to the development of schizophrenia. Methylation is a process that involves small changes to DNA that can be inherited or be the result of environmental factors such as smoking, dietary habits and medical treatment.

“DNA methylation changes over time,” said principal investigator Karolina Aberg, Ph.D., associate director of the Center for Biomarker Research and Precision Medicine and assistant professor at VCU School of Pharmacy. “Age is one aspect that changes methylation patterns, but habits like what you eat and drink and how much you exercise can also have an effect.”

 Click here to read the full press release.


 

Deep Sequencing of Three Loci Implicated in Large-Scale Genome-Wide Association Study Smoking Meta-Analyses published in Nicotine & Tobacco Research

September 2015: The Center has identified specific sets of genetic variants associated with smoking susceptibility by deep sequencing three genes previously implicated by other genome-wide association studies, as detailed in the advanced online publication of Oxford University Press journal Nicotine & Tobacco Research. In this study, we created a catalog of all genetic variants in and around these genes allowing us to examine variants not previously studied such as variants not commonly found in the population and those related to the regulation of gene expression. These findings could eventually assist in identifying new avenues to better understand and treat nicotine addiction

Click here to read the full press release.

Dr. Shaunna Clark Verhulst, Ph.D. participated in a radio interview on 88.9 WCEV September 24, 2015 discussing the results included in this paper.


 

The Center received a $3 million NIH grant to study molecular marks left by adverse events in childhood.

July 2014: Principal investigator Edwin van den Oord and co-investigator Karolina Aberg were awarded a five-year research grant of 3 million dollars by the National Institute of Mental Health. The project (R01MH104576; “Developmental methylomics of childhood trauma and its health consequences”) aims to study how early adverse experiences become biologically embedded and create long term health risks. The researchers will assay the approximately 28 million possible methylation sites in the human genome using the most recent high throughput sequencing technology. The project builds on a study started by collaborators at Duke University that began when its subjects were 9 to 13 years and is still ongoing now when the participants are adults in their 30s. Findings may help to better manage health risks later in life.

Click here to read the full press release.


 

NIMH grant was awarded to integrate methylomic profiles with genotype and gene expression information from schizophrenia cases and controls.

January 2014: Dr. Karolina A. Aberg was awarded a Small Research Grant (R03) from the National Institute of Mental Health, entitled “Mediators of Methylomic Profiles in 1500 Schizophrenia Cases and Controls”. This study takes advantage of our methylome-wide association study data that we recently published and additional phenotype and extensive genotype information is available. For this project we propose a set of novel analysis that aims to find methylation markers and further improve our understanding of the role played by methylation in SZ pathogenesis. This goal will be achieved through data integration. For this purpose we will first conduct MWAS of environmental mediators and perform methylation quantitative trait locus (meQTL) analyses exploring potential regulatory differences between SZ cases and controls. In addition to the data that is generated by performing additional MWAS and meQTL analyses, we will also include other data sets such as GWAS and genome-wide mRNA expression that are directly related to SZ or of relevance for brain function.


 

Methylome-Wide Association Study of Schizophrenia published in JAMA Psychiatry.

January 2014: The Center has performed one of the first large-scale methylome-wide association studies of schizophrenia, as detailed in the online January issue of JAMA Psychiatry. In this study, we investigated approximately 27 million DNA methylation markings in blood samples from 1,497 schizophrenia cases and controls.  The study identified 139 highly significant methylation sites. By replicating the top findings we ensured artifacts or statistical errors did not falsely cause the results. Many of the replicating markings could be linked to hypoxia, immune response and neuronal differentiation, which are risk factors previously associated with schizophrenia development. These findings suggest new avenues to better understand and treat schizophrenia.   

Click here to read the full press release.

Dr. Karolina Aberg, Ph.D. participated in a radio interview on 88.9 WCEV January 28th, 2014 discussing the results included in this paper. 


 

The Center is awarded a five-year research grant for methylation studies of Major Depressive Disorder (MDD)

September 2013: Principal investigator Edwin van den Oord and co-investigators at the Center were awarded a five-year research grant (R01) grant of 3 million dollars by the National Institute of Mental Health (R01 MH099110). The project entitled “A longitudinal methylome study to detect biomarkers predicting MDD trajectories”, aims to identify DNA methylation biomarkers that predict chronic depression. The investigation will include a genome-wide search of more than 27 million methylation sites followed by targeted replication, using a different technology, in independent samples. The project will be conducted in collaboration with the VU University in Amsterdam, the Netherlands. The potential findings may lead to a better understanding of the disease etiology, which in turn may provide the ability to improve treatment of depression.

Click here to read the full press release.


 

Upgraded configuration ensures that more next-generation sequencing data can be generated to a lower per sample cost.

September 2013: The Center is dedicated to conducting high quality research using high-technological approaches that ensures accurate and reliable results. Furthermore, to ensure that as much high quality research as possible can be performed for each research dollar the Center is dedicated to using the most cost-effective approaches available. In this spirit, the Center’s SOLiD 5500xl next-generation sequencing platform (Life Technology) has been upgraded with the latest Wildfire component. With the new configuration more data can be generated in less time to a lower per sample cost. That is, hands-on time has decreased and the average output, in number of reads, has increased. With the improved configuration more research can be performed.


 

A Comprehensive Family-Based Replication Study of Schizophrenia Genes is published in JAMA Psychiatry

April 2013: Center members (Drs. Aberg, Bukszar, McClay, Khachane and Van den Oord) led a large international collaborative study entitled, “A Comprehensive Family-Based Replication Study of Schizophrenia Genes” that was published in JAMA Psychiatry. The study involved integration of 18 genome-wide association studies (including 21,953 individuals) for schizophrenia and six other sources of data tables relevant for the disorder. The most prominent findings (8107 markers) were replicated in 6298 individuals (including 3286 cases) from 1811 nuclear families. The replication results showed highly significant enrichment of markers with small p-values and several interesting candidate genes were detected. These replication results contribute to a better understanding of the molecular and biological mechanisms involved in schizophrenia. Furthermore, these findings lay the groundwork for further experiments that may result in development of improved treatment options for schizophrenia patients.

 Click here to read the full press release.

On April 9, 2013 Dr. Edwin J.C.G. van den Oord participated in a short video interview conducted by JAMA Psychiatry to discuss the results of this study. 


 

NIMH grant to use cutting-edge DNA sequencing technology to study TCF4 - a prominent schizophrenia candidate gene.

September 2012: Dr. Joseph McClay was awarded an Exploratory / Developmental Research Grant (R21) from the National Institute of Mental Health, entitled “Functional Characterization of Pathways Regulated by Schizophrenia Gene TCF4”. Recently, large-scale genetic studies of schizophrenia have converged on several genes, and TCF4 is arguably the gene displaying the best supporting evidence of all. TCF4 is involved in the regulation of other genes, so here we propose cutting-edge DNA sequencing technologies to discover the network of genes under TCF4 control. We will then study this genetic network in multiple biological datasets of schizophrenia patients and controls, assessing genetic variation, DNA methylation and gene expression, in order to advance our understanding of how TCF4 may affect risk for the disorder.


 

Research funding to perform high coverage sequencing of 120 candidate genes for substance abuse.

June 2012: The Center was awarded a grant to sequence genes related to substance abuse and dependence in 1000 individuals using next generation technology. This project is funded through a sub-award from Duke University, as part of the research program “A developmental model of gene-environment interplay in substance use disorders” (PI: Jane Costello; Funding agency: National Institute on Drug Abuse / NIH; R01DA024413). The study will focus on alcohol, smoking and cannabis use. In total, over 120 genes will be completely sequenced at high coverage. The study aims to find genetic associations between rare and common variants and drug abuse outcome measures.


 

NIMH grant to perform integration of existing data from multiple platforms on psychiatric disorders.

May 2012. Dr. Edwin van den Oord was awarded a Research Project Grant (R01) from the National Institute of Mental Health (1R01MH097283), to perform data integration on large psychiatric datasets. The project, entitled “Cis and trans data integration to find mechanisms causing psychiatric disorders”, aims to combine data from large empirical studies and public biological databases. In particular, the project will capitalize on data releases from projects funded through the American Recovery and Reinvestment Act as they become available in 2012. The VCU research team, in close collaboration with researchers at the University of North Carolina at Chapel Hill, will focus on schizophrenia, bipolar disorder, depression and autism. The purpose of the grant is to improve understanding of how psychiatric disorders develop, and to identify potential new drug targets.


 

A Center member was awarded a training grant to study alcohol and addiction.

April 2012. Dr. Shaunna Clark received a Mentored Research Scientist Development Award (K01AA021266) from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), entitled “Investigating methylation patterns associated with alcohol use and addiction”. This prestigious NIH training award will enable Dr. Clark to perform a meta-analysis of several next generation sequencing methylation datasets focused on alcohol behaviors. The findings will be followed-up in independent samples and through studies in model organisms. The purpose of the study is to gain traction on the direction of causality in methylation studies of alcohol and to evaluate the possible use of methylated sites as biomarkers for alcoholism.


 

A Center member was awarded a training grant to study internalizing disorders.

February 2012. Dr. Daniel Adkins received a Mentored Research Scientist Development Award K01 from the National Institute of Mental Health (K01MH093731), entitled “Integrating Genomic and Environmental Perspectives on Internalizing Disorders”. This prestigious award will include data integration techniques for GWAS, gene-based, pathway-based, and polygenic “risk profile” score analyses, machine learning applications for investigating epistasis and nonlinear genomic effects, and studies of gene-environment interaction. Dr. Adkins will apply these techniques to the study of internalizing disorders in large, longitudinal datasets comprising several thousand subjects.


 

The Center is awarded a $4.5 million research grant to detect schizophrenia methylation markers

December 2010: Principal investigator Dr Edwin van den Oord and other members of the Center were awarded a two-year research grant of $4.5 million to research Schizophrenia methylation markers. The grant was awarded by the National Institute of Mental Health through the 2009 American Recovery Reinvestment Act. The research will include methylome-wide screening of 1500 case-control samples and top findings will be followed up in independent samples using a different technology. The project will be completed in collaboration with the Karolinska Institute in Stockholm, Sweden. Methylation sites can be used to determine new drug targets that can be applied in clinical settings to improve diagnosis and treatments of this devastating illness.
 
Click here to read the full press release.

 Updated August 2017