COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDER

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Bipolar affective disorder is a severe heritable condition affecting about one percent of the population. The mode of inheritance is poorly understood and probably involves multiple loci of small to moderate effect. Genetic linkage studies have not been robust although some reports of linkage have been replicated several times. The NIMH began a national archival database for search of linked genes in this condition in 1988. Its purpose was to collect a large sample of interviews and cell line from families suitable for linkage and association studied. Four centers participated in the initiative: Indiana University, Johns Hopkins University, Washington University of St. Louis, and the NIMH Intramural Program. A new structured polydiagnostic interview, the Diagnostic Interview for Genetic Studies (DIGS), was developed and field-tested. Ascertainment was begun in 1992 to identify Bipolar I (BPI) probands with a BPI or Schizoaffective, Bipolar type (SA/BP) first degree relative. Two hundred and forty-three families have been enrolled in the program including 1025 affected subjects. Twenty one hundred sixth five structured interviews have been given and 2097 immortalized cell lines have been cryopreserved. A genomic survey has been completed on 540 subjects selected from 97 families and eight candidate areas for linkage have been identified, some supporting previous findings. These cell lines and related clinical information has been publicly released. A follow-up sample is presently being genotyped, with particular attention to areas of interest identified in the original survey. It is proposed to extend the present study through families identified by a BPI-BPI sib pair at eight sites (Indiana, Washington University of St. Louis, Johns Hopkins, University of Pennsylvania, University of California, San Diego University of Utah, University of Chicago, and University of Iowa). A total of 450 new families and 2500 cell lines and interviews over the next four years will be added. This sample will be used to confirm and extend present findings of linkage, to narrow the implicated regions, and to test candidate genes. Genotypes will be shared with a consortium of investigators studying linkage in bipolar illness. Cell lines and interview data will be made freely available to the scientific community.