Bipolar disorder (BD; manic depressive illness26) refers to an episodic recurrent pathological disturbance in mood (affect) ranging from extreme elation or mania to severe depression and usually accompanied by disturbances in thinking and behaviour: psychotic features (delusions and hallucinations) often occur. Pathogenesis is poorly understood but there is robust evidence for a substantial genetic contribution to risk27,28. The estimated sibling recurrence risk (λs) is 7-10 and heritability 80-90%27,28. The definition of BD phenotype is based solely on clinical features because, as yet, psychiatry lacks validating diagnostic tests such as those available for many physical illnesses. Indeed, a major goal of molecular genetics approaches to psychiatric illness is an improvement in diagnostic classification that will follow identification of the biological systems that underpin the clinical syndromes. The phenotype definition that we have used includes individuals that have suffered one or more episodes of pathologically elevated mood (see Methods), a criterion that captures the clinical spectrum of bipolar mood variation that shows familial aggregation29.
