Evaluation of the Genetics of Bipolar Disorder

This study looks to identify genes that may affect a person's chances of developing bipolar disorder (BP) and related conditions.

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 has been reported to a number of chromosomal regions; some findings have been replicated. In 1988 the NIMH began a national archival database to search for susceptibility loci/genes in this condition. Its purpose was to collect a large sample of interviews and cell lines from families suitable for linkage and association studies. Since 1988, the NIMH-IRP has been an active site in this multi-center study. The protocol was originally supervised by Elliot Gershon, MD (1988-July 1998) and Dennis L. Murphy, MD (July 1998 - January 2004). In January 2004, Francis J. McMahon, M.D, took over supervision of the protocol. An expanded Consortium of sites concentrating on families identified through a sib pair was approved in August 1998 by the NIMH Extramural Program (MH 59535) via a competitive application. This Consortium added 450 new families and 2500 cell lines. Cell lines, clinical data, and 2 genome-wide sets of microsatellite genotypes have been made freely available to the scientific community under the auspices of the NIMH Center for Genetic Studies. In 2003, the IRB approved an amendment to expand the ascertainment criteria to include sib-pairs with a diagnosis of bipolar II disorder. Families ascertained in this manner are contributed to a second, large sample being collected in collaboration with The Johns Hopkins University and the University of Chicago, known as the CHIP study. In October 2003, the NIMH Extramural Program approved, via a competitive application, an additional 4 years of support for the Consortium collection, now including 11 extramural sites in addition to the IRP site. In this round, the focus will shift from affected sibling pairs to parent-affected offspring triads, with the goal of accruing a large sample suitable for future association studies. Both the Consortium and CHIP projects have similar study design and essentially identical recruitment, evaluation, and analysis procedures, so both projects are described together in what follows.

• Mania
• Bipolar, Disorder
• Depression
• Mood Disorder
• Schizoaffective
• Manic Depression

• Berrettini WH, Ferraro TN, Goldin LR, Weeks DE, Detera-Wadleigh S, Nurnberger JI Jr, Gershon ES. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5918-21.
• Detera-Wadleigh SD, Badner JA, Goldin LR, Berrettini WH, Sanders AR, Rollins DY, Turner G, Moses T, Haerian H, Muniec D, Nurnberger JI Jr, Gershon ES. Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q. Am J Hum Genet. 1996 Jun;58(6):1279-85.
• Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, Lathrop M, Gyapay G, Morissette J, Weissenbach J. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152-4.

• INCLUSION CRITERIA:

Age > 18 yr

Able to provide informed consent

Diagnosed with bipolar disorder not attributable to substance abuse, neurological disease; or a 1st or 2nd degree relative of an enrolled participant

Able to safely provide a blood or saliva sample

EXCLUSION CRITERIA:

Active alcohol or substance abuse