Bipolar Disorde, type 1 (BPI) is a severe mental illness that appears to be caused in part by multiple susceptibility genes, each of small effect. Detection of BPI susceptibility genes will thus likely require investigation of a very large sample of pedigrees with multiple affected cases and a focus on more genetically homogeneous populations. We will collect, over 4 years, diagnostic information and DMA samples from 385 families of Latino descent, each with a minimum of 2 siblings affected with BPI (DSM-IV diagnosis) in order to detect BPI susceptibility loci in this population. We have formed a collaboration of 7 sites throughout the Southwest United States, Mexico, and Central America to accomplish this task. Each site has professional access to a large Latino population and extensive experience in diagnosis of BPI in Latinos. Each Center will use an opportunistic recruiting mechanism to ascertain probands and families, including sources such as mental health clinics, hospitals and patient support groups. A uniform approach will be used to diagnose subjects, consisting of blinded interviews with the DIGS (Diagnostic Interview for Genetic Studies), collection of pertinent medical records and laboratory tests, and interview with a close relative of each subject. Training in accurate diagnostic assessment using the DIGS will be provided for all sites and quality control methods will be built into the course of the study. A best estimate consensus process will be used to assign final diagnoses and clinical information for each subject will be entered and stored in a centralized database. Blood samples will be obtained from all family members with a diagnosis of BPI or other, as well as from both parents and (if parents are not available), 2 other siblings. Cell cultures will be created and DMA extracted at the NIMH designated Center for Genetic Studies. In year five of this grant, a complete genome screen at an approximate density of 10 cM will be performed at CIDR (if approved). Linkage analysis based on identification of multipoint allele sharing in BPI subjects will be performed at the Southwest Foundation for Biomedical Research (SFBR). Secondary analyses will also be performed, including covariate and quantitative trait analysis, in a set of extended pedigrees containing an additional 750 subjects. Endophenotypes defined by neurocognitive and structural MRI tests related to BPI will be validated in these pedigrees and genes which contribute to these biologic variables will also be mapped through covariate quantitative trait analyses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH069856-01A2
Application #
6922660
Study Section
Special Emphasis Panel (ZRG1-GGG-H (02))
Program Officer
Lehner, Thomas
Project Start
2005-09-01
Project End
2010-06-30
Budget Start
2005-09-01
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$1,389,661
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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Sandoval, Hugo; Soares, Jair C; Mwangi, Benson et al. (2016) Confirmation of MRI anatomical measurements as endophenotypic markers for bipolar disorder in a new sample from the NIMH Genetics of Bipolar Disorder in Latino Populations study. Psychiatry Res Neuroimaging 247:34-41
Gonzalez, Suzanne; Gupta, Jayanta; Villa, Erika et al. (2016) Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort. Bipolar Disord 18:520-527
Gonzalez, Suzanne; Camarillo, Cynthia; Rodriguez, Marco et al. (2014) A genome-wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32. Am J Med Genet B Neuropsychiatr Genet 165B:479-91
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Gonzalez, Suzanne; Xu, Chun; Ramirez, Mercedes et al. (2013) Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study. Bipolar Disord 15:206-14
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Glahn, David C; Almasy, Laura; Barguil, Marcela et al. (2010) Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families. Arch Gen Psychiatry 67:168-77
Contreras, Javier; Hare, Elizabeth; Pacheco, Adriana et al. (2010) Is subclinical anxiety an endophenotype for bipolar I patients? A study from a Costa Rican sample. J Affect Disord 122:267-72