This proposal is for a three year renewal of a cooperative agreement between NIMH and participating centers at Johns Hopkins University, Indiana University and Washington University at St. Louis. The Intramural Research Program of NIMH participates under a separate mechanism. The goal of the collaboration is to assemble a large set of multiplex families with Bipolar Affective Disorder for genetic linkage studies. We have proceeded to develop a systematic ascertainment scheme to identify families with a Bipolar I (BPI) proband and a BPI or Schizoaffective Bipolar (SA/BP) first-degree relative. Additional living and available relatives are required to ensure the maximum informativeness of the sample. Non-systematically ascertained families are accepted into the study if they have four or more closely related affected individuals. A new structured interview, the Diagnostic Interview for Genetic Studies (DIGS) was developed, field-tested, and assessed for intrasite and intersite reliability. A companion instrument, the Family Interview for Genetic Studies (FIGS) was also developed as part of this program. A central Data Management Center (DMC) archives diagnostic information, and a National Cell Repository stores genetic material. At this point, 115 families have been identified at the four sites. About 65% of these have been systematically ascertained. These families include 495 persons with major affective disorder among 1656 living members. Eight hundred thirty- five subjects have been directly interviewed, and 767 persons have had blood samples sent to the Cell Repository for transformation. Simulation studies show that the existing sample is capable of detecting a single locus under conditions of 50% heterogeneity, and that the projected sample (220 families with 2200 cell lines) will likely detect a locus responsible for illness in only 25% of the families. This renewal proposes the completion of the already ascertained families, the continuing ascertainment of new families until the projected total is reached, and the clinical follow-up of participants to ensure the maximum phenotypic validity of the sample. The follow-up study will enable course of illness to be included as a nosological variable, provide incident cases and newly informative branches of pedigree and reduce the loss of power resulting from instability of diagnosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01MH046280-07
Application #
2246981
Study Section
Special Emphasis Panel (SRCM (03))
Project Start
1989-09-30
Project End
1997-08-31
Budget Start
1995-09-30
Budget End
1996-08-31
Support Year
7
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Swaminathan, Shanker; Koller, Daniel L; Foroud, Tatiana et al. (2015) Characteristics of Bipolar I patients grouped by externalizing disorders. J Affect Disord 178:206-14
Jacobsen, Kaya K; Nievergelt, Caroline M; Zayats, Tetyana et al. (2015) Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder. J Affect Disord 172:453-61
Leonpacher, A K; Liebers, D; Pirooznia, M et al. (2015) Distinguishing bipolar from unipolar depression: the importance of clinical symptoms and illness features. Psychol Med 45:2437-46
Monahan, P O; Stump, T; Coryell, W H et al. (2015) Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity. Psychol Med 45:2181-96
Graae, Lisette; Paddock, Silvia; Belin, Andrea Carmine (2015) ReMo-SNPs: a new software tool for identification of polymorphisms in regions and motifs genome-wide. Genet Res (Camb) 97:e8
Winham, Stacey J; Cuellar-Barboza, Alfredo B; McElroy, Susan L et al. (2014) Bipolar disorder with comorbid binge eating history: a genome-wide association study implicates APOB. J Affect Disord 165:151-8
Li, Cong; Yang, Can; Gelernter, Joel et al. (2014) Improving genetic risk prediction by leveraging pleiotropy. Hum Genet 133:639-50
Bigdeli, T Bernard; Maher, Brion S; Zhao, Zhongming et al. (2013) Association study of 83 candidate genes for bipolar disorder in chromosome 6q selected using an evidence-based prioritization algorithm. Am J Med Genet B Neuropsychiatr Genet 162B:898-906
Greenwood, Tiffany A; Bipolar Genome Study (BiGS) Consortium; Kelsoe, John R (2013) Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder. PLoS One 8:e53804
Jackson, Kia J; Fanous, Ayman H; Chen, Jingchun et al. (2013) Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder. Psychiatr Genet 23:20-8

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