Beps - Berlin Psychosis Study

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 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 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.