- Email: [email protected]
Beps - Berlin Psychosis Study
S466
Abstracts of the XXIV World Congress of Psychiatric Genetics (WCPG) 2016
= 4.0e-2), and contained five miRNAs and 501 mRNA genes. Six TFs also served as hub genes in these modules (POU2F1, EPAS1, PAX6, ZNF423, SOX5 and SOX9). The co-expression-suggested regulatory relationships were consistent with the binding relationships predicted by databases. Focusing on those regulations containing TFs and miRNAs, we resolved a regulation cascade from SNP variants (rs16853832) to TF (POU2F1) to miRNA (hsa-mir-320e) to target genes (NR2E1) and ultimately, to disease risks. Discussion: We revealed POU2F1 as a key regulator in a neuron differentiation/developmental module associated with disease, and revealed a putative cascade regulation effect. This study showed that we can utilize multidimensional data to construct co-expression networks. Causal relationships can be resolved among SNPs, regulatory molecules and their downstream target genes through data integration. Novel genes and their corresponding regulations underlying the disease risks could be revealed.
Disclosure Nothing to Disclose. http://dx.doi.org/10.1016/j.euroneuro.2016.09.541
Turkey (n = 14). The cases subsample reported disease related hospitalalization between 1 and 40 stays (MV = 4.02 ; SD = 5.58). Amongst the healthy controls no participant reported a lifetime or family history of schizophrenia or bipolar disorder. Age, gender and level of education differ significantly between the two subsamples. Patients were older (MVcases = 41.89 years, SDcases = 11.87 years, MVcontrols = 35.85 years, SDcontrols = 14.08 years, p o .05), more likely men (p = .018) and reported a lower level of school education (MVcases = 10.62 years, SDcases = 2.48 years, MVcontrols = 12.02 years, SDcontrols = 1.31 years, po.05) than the healthy control subsample. Discussion: The main goal of this study is to further assess the biological mechanisms of schizophrenia via combining big meta analyses of genome-wide analysis studies with costly imaging genetics or pharmacologic studies. In fact, this study will have the potential to overcome the scientific limitations of both approaches and thus, give answers to many open questions regarding the biological and epidemiological mechanisms underlying schizophrenia. Our pilot data confirms formerly reported epidemiologic data. We hope to have received genotypic data till October for this pilot sample and to report first GWAS results. The final total sample of 5000 participants will be contributed to the psychiatric genomics consortium for it’s newest GWAS meta analyses. Based on our experience, BEPS will yield to approximately 10 new genome-wide significant genetic associations.
T54. BEPS - BERLIN PSYCHOSIS STUDY
Nora Skarabis1, Stephan Ripke2 1
Charite University Hospital 2 MGH Background: Over the past decade, genome-wide association studies (GWAS) have provided fundamental insights into the genetic architecture of schizophrenia with the identification of more than 100 risk loci and the discovery that common and rare variants contribute to a very complex genetic predisposition. However, these ground-breaking discoveries come with the realisation that the identification of risk loci is merely the start of a long process towards meaningful biological understanding. To clarify how the identified risk loci actually drive the pathophysiology of schizophrenia, we want to combine successful GWAS strategies with costly imaging or even pharmacologic studies, in order to improve power with a genotype based recruiting process. Methods: As a first step, we want to recruit a new large case-control sample comprising 2500 individuals with schizophrenia and 2500 healthy controls from Berlin, Germany. As a second step, we will calculate a variety of distinct genetic risk scores (GRS) for all participants and re-invite cases and controls with particularly high or low genetic risk profiles. These then will be evaluated with detailed, deep phenotyping strategies. Results: Our pilot study comprises 82 cases with schizophrenia and 86 healthy controls. Parents and grandparents of our probands come from central Europe (n = 146) or
Disclosure Nothing to Disclose. http://dx.doi.org/10.1016/j.euroneuro.2016.09.542
T55. THE GENETIC BASIS OF THE COMORBIDITY BETWEEN CANNABIS USE AND MAJOR DEPRESSION
Karen Hodgson1, Laura Almasy2, Emma Knowles3, Jack Kent4, Joanne Curran2, Thomas Dyer2, Harald Goring5, Rene Olvera6, Mary Woolsey6, Ravi Duggirala2, Peter Fox6, John Blangero2, David Glahn7 1
Yale University School of Medicine University of Texas Rio Grande Valley 3 Yale University 4 Texas Biomedical Research Institute 5 South Texas Diabetes and Obesity Institute 6 University of Texas Health Science Center San Antonio 7 Yale University and Olin Neuropsychiatric Research Center 2
Background: While the prevalence of major depression is known to be elevated amongst cannabis users, the causes of
Abstracts of the XXIV World Congress of Psychiatric Genetics (WCPG) 2016
= 4.0e-2), and contained five miRNAs and 501 mRNA genes. Six TFs also served as hub genes in these modules (POU2F1, EPAS1, PAX6, ZNF423, SOX5 and SOX9). The co-expression-suggested regulatory relationships were consistent with the binding relationships predicted by databases. Focusing on those regulations containing TFs and miRNAs, we resolved a regulation cascade from SNP variants (rs16853832) to TF (POU2F1) to miRNA (hsa-mir-320e) to target genes (NR2E1) and ultimately, to disease risks. Discussion: We revealed POU2F1 as a key regulator in a neuron differentiation/developmental module associated with disease, and revealed a putative cascade regulation effect. This study showed that we can utilize multidimensional data to construct co-expression networks. Causal relationships can be resolved among SNPs, regulatory molecules and their downstream target genes through data integration. Novel genes and their corresponding regulations underlying the disease risks could be revealed.
Disclosure Nothing to Disclose. http://dx.doi.org/10.1016/j.euroneuro.2016.09.541
Turkey (n = 14). The cases subsample reported disease related hospitalalization between 1 and 40 stays (MV = 4.02 ; SD = 5.58). Amongst the healthy controls no participant reported a lifetime or family history of schizophrenia or bipolar disorder. Age, gender and level of education differ significantly between the two subsamples. Patients were older (MVcases = 41.89 years, SDcases = 11.87 years, MVcontrols = 35.85 years, SDcontrols = 14.08 years, p o .05), more likely men (p = .018) and reported a lower level of school education (MVcases = 10.62 years, SDcases = 2.48 years, MVcontrols = 12.02 years, SDcontrols = 1.31 years, po.05) than the healthy control subsample. Discussion: The main goal of this study is to further assess the biological mechanisms of schizophrenia via combining big meta analyses of genome-wide analysis studies with costly imaging genetics or pharmacologic studies. In fact, this study will have the potential to overcome the scientific limitations of both approaches and thus, give answers to many open questions regarding the biological and epidemiological mechanisms underlying schizophrenia. Our pilot data confirms formerly reported epidemiologic data. We hope to have received genotypic data till October for this pilot sample and to report first GWAS results. The final total sample of 5000 participants will be contributed to the psychiatric genomics consortium for it’s newest GWAS meta analyses. Based on our experience, BEPS will yield to approximately 10 new genome-wide significant genetic associations.
T54. BEPS - BERLIN PSYCHOSIS STUDY
Nora Skarabis1, Stephan Ripke2 1
Charite University Hospital 2 MGH Background: Over the past decade, genome-wide association studies (GWAS) have provided fundamental insights into the genetic architecture of schizophrenia with the identification of more than 100 risk loci and the discovery that common and rare variants contribute to a very complex genetic predisposition. However, these ground-breaking discoveries come with the realisation that the identification of risk loci is merely the start of a long process towards meaningful biological understanding. To clarify how the identified risk loci actually drive the pathophysiology of schizophrenia, we want to combine successful GWAS strategies with costly imaging or even pharmacologic studies, in order to improve power with a genotype based recruiting process. Methods: As a first step, we want to recruit a new large case-control sample comprising 2500 individuals with schizophrenia and 2500 healthy controls from Berlin, Germany. As a second step, we will calculate a variety of distinct genetic risk scores (GRS) for all participants and re-invite cases and controls with particularly high or low genetic risk profiles. These then will be evaluated with detailed, deep phenotyping strategies. Results: Our pilot study comprises 82 cases with schizophrenia and 86 healthy controls. Parents and grandparents of our probands come from central Europe (n = 146) or
Disclosure Nothing to Disclose. http://dx.doi.org/10.1016/j.euroneuro.2016.09.542
T55. THE GENETIC BASIS OF THE COMORBIDITY BETWEEN CANNABIS USE AND MAJOR DEPRESSION
Karen Hodgson1, Laura Almasy2, Emma Knowles3, Jack Kent4, Joanne Curran2, Thomas Dyer2, Harald Goring5, Rene Olvera6, Mary Woolsey6, Ravi Duggirala2, Peter Fox6, John Blangero2, David Glahn7 1
Yale University School of Medicine University of Texas Rio Grande Valley 3 Yale University 4 Texas Biomedical Research Institute 5 South Texas Diabetes and Obesity Institute 6 University of Texas Health Science Center San Antonio 7 Yale University and Olin Neuropsychiatric Research Center 2
Background: While the prevalence of major depression is known to be elevated amongst cannabis users, the causes of