My group is interested in identifying and characterising genes which increase risk to mental illness, particularly bipolar disorder and schizophrenia. While these are clinically distinct disorders, bipolar disorder and schizophrenia share a common genetic foundation, as well as overlapping constellations of symptoms. Understanding the genetic contributors to mental illness enable us to improve our understanding of the biological basis of these psychiatric conditions, identify similarities and differences across disorders, and ultimately improve treatment of psychiatric disorders through these discoveries. Identifying the specific genes which are impaired in mental illness also helps to demystify the functioning of the human brain, and to comprehend the orchestration of events which leads to development of a healthy or unhealthy brain.

Genetic and epigenetic contributors to bipolar disorder in a high risk cohort

The offspring of individuals with bipolar disorder are at increased risk of mental illness, but our tools to predict which of these genetically at-risk young people will eventually develop disorder are very imprecise. Longitudinal studies that ascertain at-risk participants and monitor them prospectively are an effective approach for identifying early clinical and biological markers of future illness. This study examines genomic risk load of genetic and epigenetic factors, early structural brain changes and clinical information to determine if we can use biological signatures to predict which individuals will ultimately transition to illness, and identify targets for intervention prior to onset of symptoms which lead to a clinical diagnosis.

Genetic contributors, clinical course and pharmacogenomics of Bipolar Disorder in a large population cohort

Bipolar Disorder is a severe and debilitating psychiatric condition, for which the clinical course is highly variable between individuals, and the specific genetic causes remain largely obscure. This landmark study aims to use linked administrative health record data and state-of-the-art genomics technologies to address four key knowledge gaps: 1) identification of genes and molecular pathways which increase risk of illness; 2) pharmacogenomics studies to identify genetic signatures which may predict responsiveness to commonly used medicinal treatments; 3) examination of the impact of rare disruptive genetic variants on disease severity; and 4) consideration of the genetic correlates of both the course and severity of illness, and relationships to general medical conditions which more commonly present in people with bipolar disorder (such as cardiovascular disease, type II diabetes and asthma) and which further reduce quality of life and significantly impact overall health of people living with this condition.

Investigation of rare variants which increase risk to bipolar disorder in families with a high density of illness

Advances in technology have enabled sequencing at the level of the entire genome to become a reality. We have access to number of rare families with highly heritable forms of bipolar disorder, for which we will apply this powerful technology to identify specific genetic factors which increase disease risk. We assess loss-of-function variation within genes, at both the level of single base mutations and variation in gene copy number, which track with illness in these families to identify new genes which contribute to illness.

International collaborative consortia involvement

We are active contributors to a number of large international collaborative studies, including the Psychiatric Genomics Consortium (PGC), the Bipolar Sequencing Consortium (BSC), the Bipolar High Risk Consortium, and have contributed to a number of projects through the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortia. These efforts aim to identify risk genes which contribute to disease, and examine their effect on brain structure, function and disease.