The goal of this revised renewal project is to genotype and analyze the family resources the investigators have already ascertained and clinically assessed in order to elucidate the genetics of bipolar affective disorder. To-date, this study has carefully evaluated, by direct interviews with psychiatrists, 52 families containing multiple affected individuals who were initially ascertained through a treated bipolar I (BPI) proband. The investigators' goal is to produce an 8 cM genetic map in these families, using highly polymorphic simple sequence repeat markers. This proposed effort will provide the sole source of funding for the remaining 55 percent of genotypes required to achieve the overall project goal. Genetic analyses include non-parametric (affected sib-pair and affected pedigree member) and parametric (likelihood) analyses. These analyses consider both dominant and recessive models of transmission. Further analyses such as the transmission disequilibrium test are planned for the completed data set. The study efforts to-date have uncovered evidence for genetic linkage of bipolar disorder to markers on chromosome 18. The investigators' evidence supports the findings on 18p, although data from the current study implicate a larger region. The applicants have found an effect of the sex of the affected parent with a maximum LOD score of 3.6 (D18S41) when the disease locus segregates through the paternal lineage. The unaffected, uncertain, and recurrent unipolar individuals will continue to be followed-up clinically on an annual basis.
| 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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