This competing renewal of an Independent Investigator Career Development Award (K02) aims to expand the candidate's research expertise in genetic studies of cannabis involvement in two main areas: (a) integration of neuroimaging with emerging genomic results for cannabis involvement; and (b) new methodology for genomic (meta) analyses, in particular, understanding how genomic factors influence the comorbidity between cannabis involvement and psychiatric as well as psychosocial correlates. She will also work closely with leaders in the field of big data psychiatric genetics to expand her expertise in managing consortia, developing novel collaborations, expanding her work in a clinical direction and in dissemination and community engagement. In addition, the candidate will continue to mentor trainees in addiction and genomic methods and maintain her training in responsible conduct of research. The overarching goal of this K02 is to provide the candidate, a tenured Associate Professor, with protected time to conduct research on parsing the role of genetic influences on cannabis involvement. The public health significance of this research is particularly timely as a wave of legislative change surrounding the status of recreational cannabis sweeps the nation and scientific interest in the deleterious correlates and consequences of cannabis use intensifies. The candidate's research portfolio is amongst the few that is primarily focused on genetically informed studies of cannabis involvement and continues to inform this research debate with empirical findings. With support from the first phase of funding, the candidate published numerous peer-reviewed studies, and generated findings documenting (a) new loci for cannabis use disorders (CUD), (b) the role of childhood abuse on genetic risk for CUD and (c) polygenic approaches to genetic dissection of variance in CUD. She has also renewed her existing R01 and secured funding for two additional R01s. Most recently, she co-established the Psychiatric Genomics Consortium's Substance Use Disorders (PGC-SUD) workgroup, a new addition to the PGC repertoire of highly powered genomewide association meta-analytic studies. The next phase of training and collaboration will extend the candidate's expertise in one existing (genomics) and one novel (neurogenetics) direction. First, via involvement in the PGC, the candidate will master the most recently developed genomic methods, including integrated approaches for bioinformatics and epigenome annotation. This will solidify her knowledge in modern genomic methods and allow her to develop the PGC-SUD group as the foremost source for high quality SUD genetics research. Second, the candidate will gain proficiency in neuroimaging and imaging genetics approaches to begin to integrate her genomic discoveries with neurobiological correlates. This will effectively position the candidate to propose cutting-edge imaging genetics research applications. Overall, continued funding will result in high-quality, peer-reviewed publications that will contribute to the public debate regarding the etiology, progression and consequences of the use of cannabis, a highly popular psychoactive substance.

Despite strong evidence for heritable variation in cannabis involvement, there has been limited research directed at identifying loci, genes and pathways that underpin this heritability. Furthermore, linking genetic findings to neurobiological correlates would provide a more comprehensive overview of the biology underlying cannabis involvement and, in concert, these approaches could strongly inform how cannabis involvement is related to mental health and psychosocial outcomes. These research objectives form the core goals of this K02 competing renewal and are particularly relevant to the current public debate surrounding recreational cannabis use in the United States.