This is a renewal of a project to develop (and share with other investigators) a highly informative resource of bipolar, type I (BPI) families to test for linkage to marker loci spanning the human genome and to candidate genes. In order to achieve our purposes we continue to 1) examine families, ascertained through a proband with BPI with two or more affected sibs (or with one affected sib and one affected parent); 2) establish lymphoblastoid lines on all participating family members; 3) analyze the variations in clinical features between and within families; and 4) employ informative genetic markers spanning the human genome in order to conduct linkage analyses. The clinical investigators at Johns Hopkins, assisted by consultants at the University of Iowa, are conducting an intensive screening program to ascertain only highly suitable, unilineal bipolar families. After two years of study, over 1600 BPI families have been screened and rejected. Of the remaining 96 families, 17 unilineal BPI families are suitable and are completely clinically assessed. We anticipate completing 25 such families by the end of Year 3 of the original grant. We are asking for funds in this renewal proposal to ascertain and study sufficient families to yield another 25 unilineal BPI families, and to complete DNA studies, linkage analyses, and clinical analyses on a final set of 50 unilineal BPI families. We will use a systematic RFLP linkage map of the human genome, probes for candidate loci, newer PCR-derived probes, and karyotypes to search for relevant loci. Our consultant, Dr. Eric Lander, has developed newer methods for linkage analysis for complex disorders, which we will employ in addition to more standard linkage analyses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH042243-05
Application #
3381422
Study Section
Special Emphasis Panel (SRCM (02))
Project Start
1988-07-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Tighe, Sarah K; Reading, Sarah A; Rivkin, Paul et al. (2012) Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives. Bipolar Disord 14:888-93
Nwulia, E A; Hipolito, M M; Aamir, S et al. (2011) Ethnic disparities in the perception of ethical risks from psychiatric genetic studies. Am J Med Genet B Neuropsychiatr Genet 156B:569-80
Mielke, M M; Zandi, P P; Shao, H et al. (2010) The 32-year relationship between cholesterol and dementia from midlife to late life. Neurology 75:1888-95
Goes, Fernando S; Willour, Virginia L; Zandi, Peter P et al. (2009) Family-based association study of Neuregulin 1 with psychotic bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 150B:693-702
Grover, Deepak; Verma, Ranjana; Goes, Fernando S et al. (2009) Family-based association of YWHAH in psychotic bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 150B:977-83
Maheshwari, Manjula; Shi, Jiajun; Badner, Judith A et al. (2009) Common and rare variants of DAOA in bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 150B:960-6
Willour, V L; Chen, H; Toolan, J et al. (2009) Family-based association of FKBP5 in bipolar disorder. Mol Psychiatry 14:261-8
Zandi, Peter P; Belmonte, Pamela L; Willour, Virginia L et al. (2008) Association study of Wnt signaling pathway genes in bipolar disorder. Arch Gen Psychiatry 65:785-93
Potash, James B; Buervenich, Silvia; Cox, Nancy J et al. (2008) Gene-based SNP mapping of a psychotic bipolar affective disorder linkage region on 22q12.3: association with HMG2L1 and TOM1. Am J Med Genet B Neuropsychiatr Genet 147B:59-67
Potash, James B; Toolan, Jennifer; Steele, Jo et al. (2007) The bipolar disorder phenome database: a resource for genetic studies. Am J Psychiatry 164:1229-37

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