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Genetic studies of bipolar affective disorder in large families

¹ Department of Psychiatry, University of Edinburgh
² Institute of Cell, Animal and Population Biology, University of Edinburgh, UK

Correspondence: Professor D. H. R. Blackwood, University of Edinburgh Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh EH10 5HF, Scotland, UK. Tel: +44 (0)131 537 6000; fax: +44 (0)131 537 6259; e-mail: dblackwood{at}ed.ac.uk

Declaration of interest This work was supported by a grant from the Chief Scientist's Office, Scottish Executive.

Background Genetic factors are known to be important in the aetiology of bipolar disorder.

Aims To review linkage studies in extended families multiply affected with bipolar disorder.

Method Selective review of linkage studies of bipolar disorder emphasising the gains and drawbacks of studying large multiply-affected families and comparing the statistical methods used for data analysis.

Results Linkage of bipolar disorder to several chromosome regions including 4p, 4q, 10p, 12q, 16p, 18q, 21q and Xq has first been reported in extended families. In other families chromosomal rearrangements associated with affective illnesses provide signposts to the location of disease-related genes. Statistical analyses using variance component methods can be applied to extended families, require no prior knowledge of the disease inheritance, and can test multilocus models.

Conclusion Studying single large pedigrees combined with variance component analysis is an efficient and effective strategy likely to lead to further insights into the genetic basis of bipolar disorders.