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 state-of-the-art whole genome sequencing technology 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. The Sax Institute’s ​“45 and Up” Study is an exceptionally powerful resource of over 267,000 men and women across NSW, from which we intend to recruit and obtain genetic samples from ~1,200 individual participants for this study. This study will bring together researchers from the Black Dog Institute, UNSW Centre for Big Data Research in Health, Prince of Wales Hospital and the Sax Institute, with sequencing to be performed at the Kinghorn Centre for Clinical Genomics with support from the NSW Ministry of Health. This study will also contribute to key international collaborative efforts to further potential for gene discovery, improving our understanding of the causes of this complex and highly heritable genetic condition.