Genetic Basis of
Psychiatric Disorders


A significant focus of The Smoller Lab’s research portfolio is elucidating the genetic basis of childhood and adult-onset psychiatric disorders across the spectrum of psychopathology. Genetic liability is the best-established risk factor for neuropsychiatric disorders, but identifying the genes involved has been challenging due to their genetic and phenotypic complexity. Through research in our lab, and in collaboration with colleagues from around the world including through the Psychiatric Genomics Consortium (PGC), we have helped lead the discovery of genetic variants contributing to a large range of psychiatric disorders. We also have a strong interest in cross disorder genetics and pleiotropy, as well as their implications for psychiatric nosology.


Cross Disorder Genetics (CDG) of Psychiatric Disorders
Dr. Smoller is co-chair of the Cross Disorder Workgroup (CDG) of the Psychiatric Genomics Consortium (PGC). The PGC goal is “to unite investigators around the world to conduct meta- and mega-analyses of genome-wide genomic data for psychiatric disorders.” The CDG aims to identify genetic relationships across and between childhood and adult onset psychiatric disorders including autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, schizophrenia, obsessive compulsive disorder, Tourette’s Syndrome, anxiety disorders, substance use disorders, post-traumatic stress disorder and others. This research uses common and rare variant association methods as well as polygenic approaches (including polygenic risk scores, SNP heritability methods and genetic correlation analysis) and bioinformatics/functional genomics.
Genetic and environmental contributions to risk and resilience for suicide, PTSD, depression, and other stress related disorders

We collaborate with colleagues in the National Institutes of Mental Health (NIMH) funded Army STARRS project, a large study involving research teams all over the country, with the overarching goal of preventing suicide among soldiers. With our colleagues, we have conducted genome-wide association studies focusing on PTSD, suicidal behavior, depression, and social anxiety. In addition, we have used large-scale data resources to study the genetic and environmental basis of resilience and protective factors for depression and other mental health conditions. This has included using genomics to prioritize and validate actionable preventive factors (e.g. physical activity, social support).

International Cohort Collection for Bipolar Disorder
We have helped lead this international consortium with colleagues at the Broad Institute, USC, Cardiff University, Mount Sinai School of Medicine, and the Karolinka Institutet. The goal has been to foster discoveries in the genetics of bipolar disorder by developing and applying high-throughput phenotyping methods, conducting genomewide association analyses, identifying disorder subtypes, expanding the diversity of bipolar genetic research, and providing tools for further discovery in the scientific community.
The Development and Neural Bases of Emotion Processing
This collaboration with Boston Children’s Hospital seeks to study the nature and neural architecture of emotion processing across the first seven years of life. Targeting functional gene polymorphisms, genomewide genotyping, and telomere lengths in subjects, we seek to evaluate the impact of genetic variations on individual differences in emotion processing and its development. Genetic evaluation and the repeated measurement of neural, behavioral, and environmental parameters assesses the influence of basic emotion perception capacities on developmental trajectories.
Understanding the Connections among Genes, Environment, Family Processes and Mental Health

In collaboration with William G. Axinn, PhD and colleagues at the University of Michigan, we aim to identify key predictors of psychiatric disorders in a large population-based sample of South Asian families and communities. This collaboration is part of an existing 20-year study (the Chitwan Valley Family Study) that has included more than 10,000 individuals from 2,700 households in Nepal. Combining detail phenotypic assessment, measures of environmental exposures, and genome-wide analyses, we are examining the role of genetic and sociodemographic antecedents on risk and resilience for important mental health outcomes.

Understanding the role of a polymorphic DNA repeat at the CACNA1C gene in Bipolar Disorder
Led by Dr. Ricardo Mauro Pinto, the goal of this project, supported by Harvard Brain Science Initiative, is to apply novel genomic assays to characterize a large intronic tandem repeat in CACNA1C, a gene robustly associated with bipolar disorder. We will characterize this variants in patients with bipolar disorder and in post-mortem brain tissue.

Our Funding and Collaborative Partners


Massachusetts General Hospital
Simches Research Building
185 Cambridge Street
Boston, MA 02114