Data Analysis with GWAS and Web Database Development Towards Understanding Pleiotropy and Genetic Relationships Between Neuropsychiatric Disorders

Abstract

Advances in genome wide association studies (GWAS) are revolutionizing the field of psychiatric genetics, allowing researchers to examine the genetic basis of mental illnesses. Several risk loci have been discovered, showing genome-wide risk sharing is pervasive across many mental disorders. Identification, characterization, and clinical translation of pleiotropic effects provide fundamental insight into the genetic architecture of neuropsychiatric disorders. Yet, few data resources are available to facilitate the systematic investigation of the pleiotropic landscape in common and complex brain disorders. The upBrainGenomics (Understanding Pleiotropy of Brain Disorders using Genomics Data) database is dedicated to the investigation of genetic pleiotropy underlying 20 psychiatric and neurological disorders. Genetic relationships of the disorders were estimated based on SNP-based genome-wide genetic correlations and pathway-based genetic similarities. The web interface provides the analysis results using Heatmap Charts or Network Diagrams, which users can save in multiple file formats. Locus-specific pleiotropic information is also presented, summarizing genes and pathways with shared risk effects across 20 brain disorders. The upBrainGenomics database will enable rapid dissemination of cross-disorder GWAS results to researchers in the neuropsychiatric genetics field, and facilitate translation of genomic discoveries into understanding of brain health and precision medicine. The upBrainGenomics can be accessed at: mybrain.mgh.harvard.edu/.