Psychiatric Genomics Consortium: Mechanisms and Translation

About This Grant

The Psychiatric Genomics Consortium (PGC) has been at the forefront of psychiatric genetics for nearly two decades, massively advancing our understanding of the genomic underpinnings of psychiatric disorders. Building on its success with over 1,700 investigators and 755 impactful publications, the PGC proposes a new phase to harness the forthcoming influx of genetic and functional genomic data from across the US and around the world. This effort aims to deepen understanding of the genetic architecture of psychiatric disorders, address critical gaps in biological mechanisms, catalyze clinical relevance, and accelerate training and outreach on how genetic factors contribute to mental and physical health. We propose three synergistic Specific Aims: (1) Identify genetic variants associated with serious psychiatric disorders that afflict many Americans by rigorous integration and analysis of all available datasets using state-of-the-art methods to analyze common, rare, and structural variants. (2) Dissect heterogeneity of psychiatric and chronic medical disorders by examining shared and distinct genetic influences on risk. (3) Advance mechanistic understanding of psychiatric risk and resilience by fine-mapping genetic loci, identifying relevant biological contexts, and integrating functional genomic annotations. These aims create a cohesive framework where foundational discovery (Aim 1) informs efforts to resolve heterogeneity (Aim 2), and then to elucidate biological mechanisms (Aim 3). We will achieve these aims by leveraging our established analytical infrastructure and efficient organizational structure. This phase of the PGC will drive collaboration, accelerate genetic discovery, and deliver biological and clinical insights into psychiatric disorders, with the ultimate goal of improving patient outcomes. Including foreign sites is scientifically essential: the sample sizes required to detect genetic variants of small effect, variants that can have major public health implications for Americans, can only be achieved through global collaboration and our discoveries will accelerate genetic insights that benefit US patients.