Biological insights from 108 schizophrenia-associated genetic loci

6^th International Conference on Genomics & Pharmacogenomics

September 12-14, 2016 Berlin, Germany

Stephan Ripke

Broad Institute, Germany

Posters & Accepted Abstracts: J Mol Genet Med

Abstract :

The PGC (Psychiatric Genomics Consortium) is an international group of researchers whose major aim is to maximize the utility of extant psychiatric GWAS through mega-analysis. In a previous study, our first wave of genome-wide schizophrenia association analysis identified multiple loci involved in this genetically complex and clinically heterogeneous disorder. Here we present an update of the biological insights gained analyzing the results. This international endeavor now comprises 35,476 schizophrenia cases and 46839 controls coming from 52 sub-studies. The presented data is imputed into 1000 Genomes (Aug, 2012) and analyzed using standard logistic regression with ancestry components as covariates. All index SNPs with a p-value smaller than 1Ã?Â?10-6 were used for replication lookup in an independent GWAS analysis with 1500 cases and 66000 controls. There are numerous follow up analysis being performed with more than 100 reliably associated regions from this newest round of meta-analysis. The loci implicated include prior findings (MIR137, CACNA1C and ZNF804A) along with a host of new targets. Associations at DRD2 and multiple genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia. Additionally the hypothesized link between the immune system and schizophrenia is supported by these associations. These results are in line with prior predictions and developments in other complex disease GWAS with sufficiently large samples like Crohn's disease. They continue to provide new insights into the biology of schizophrenia.

Biography :

Email: sripke@broadinstitute.org