Integrative Mental Health Laboratory, the IMHL
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Discovering Cell Types for Psychiatric Disorders
Recently accepted for publication in Nature Neuroscience, this work -- for the first time -- maps hundreds of human brain cell types to psychiatric disorders and other complex brain phenotypes including schizophrenia, depression, bipolar disorder, alcohol consumption, sleep duration, Alzheimer's disease and multiple sclerosis.
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Sex and Gender Effects
Most psychiatric disorders have pronounced sex/gender differences in prevalence. Despite decades of research, the causes of these differences are not well understood. Using novel approaches and larger datasets we are able to tackle longstanding questions in this area. Our ongoing investigations include: genome wide association studies (GWAS) and genetic correlation analyses of hormone related traits and their relationships to psychiatric disorders, polygenic scoring analyses to detect differences in vulnerability to PTSD genetic risk in specific populations, and translational studies of hot flash genetics and neurobiology (see below)
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Hot Flash GWAS: Demonstration of Translation
One of the biggest challenges in human genetics of complex brain phenotypes has been the translation of GWAS results into neurobiological and clinical discoveries. Using hot flashes as a case example, we demonstrate how our novel cell type analyses readily recapitulate known findings about hot flash neurobiology and treatment.
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Trans-Ancestry Genetic Analyses
Most genetic research has been conducted on European ancestry populations. The transferability of results to more diverse populations is one of the most important topics in genetics right now, and we have a proven track record of publishing genetic analyses with diverse populations, and also raising awareness through analytical benchmarking of representation. Current work in this area is supported by NIH through a Population Health Sciences Spectrum Pilot Grant on Quantifying Individual Genetic Risk in Diverse Populations.
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Genome-scale analyses, international consortia
The biggest discoveries in modern genetics are often carried out by international consortia. Alternatively, they may rely on data resources from international efforts such as the 1000 Genomes Project. We work closely with the Psychiatric Genomics Consortium (PGC), which is is the world’s largest group of researchers focused on the genetics of psychiatric disorders (with 800+ members to date). Dr. Duncan led the analysis and writing of flagship papers for both the PTSD and Anorexia groups of the PGC. Projects focused on schizophrenia employed pathway analyses on both GWAS and sequence data to identify relevant biological processes and cell types.