Abstract

The investigators will study a relatively genetically homogeneous population to test the hypotheses that genetic factors are linked to bipolar disorder. The study will focus on the population of the Azores, a nine island archipelago in the Atlantic Ocean. The Azores have a centralized health system. All ten psychiatrists on the islands are collaborating with the investigators on this project. The investigators are currently funded to study schizophrenia in this same population and believe that it is critical to study all of the patients suffering with bipolar including over 300 affected family members. The pilot study has already identified 25 families with 84 affected members. A complementary strategy will be used to study candidate loci. They will study a sample of 225 subjects suffering from bipolar disorder and their parents (Total n=675) employing the haplotype relative risk and the transmission/disequilibrium test strategies. This strategy insures that the investigators control for all ancestry for each subject, using the uninherited haplotype derived from the two parents. The third sample will include all other Azorean patients with bipolar disorder in the Azores. This will be a valuable sample for assessing the prevalence of any mutations that are identified in the population. These complementary strategies will allow them to cross validate any positive results. The careful diagnostic definition of phenotype will be based on detailed structured clinical data employing the diagnostic interview for genetic studies (DIGS), which they have translated into Portuguese. The project is designed to capture a very complete history of the patient's illness, as well as to be able to follow most subjects prospectively for a long period of time. This will be extremely valuable for achieving diagnostic certainty, and minimizing false positives. The Whitehead/MIT Center for Genome Research will perform a genome-wide scan and collaborate on all data analysis for the project.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH058693-04
Application #
6588768
Study Section
Genome Study Section (GNM)
Program Officer
Moldin, Steven Owen
Project Start
2002-03-01
Project End
2004-07-31
Budget Start
2002-03-01
Budget End
2002-07-31
Support Year
4
Fiscal Year
2001
Total Cost
$673,000
Indirect Cost

  Institution

Name
Upstate Medical University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210

  Publications

Franke, Barbara; Stein, Jason L; Ripke, Stephan et al. (2016) Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nat Neurosci 19:420-431
Lee, S Hong; DeCandia, Teresa R; Ripke, Stephan et al. (2012) Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat Genet 44:247-50
Fanous, Ayman H; Middleton, Frank A; Gentile, Karen et al. (2012) Genetic overlap of schizophrenia and bipolar disorder in a high-density linkage survey in the Portuguese Island population. Am J Med Genet B Neuropsychiatr Genet 159B:383-91
Drago, Antonio; Giegling, Ina; Schäfer, Martin et al. (2012) No association of a set of candidate genes on haloperidol side effects. PLoS One 7:e44853
Machado-Vieira, Rodrigo; Pivovarova, Natalia B; Stanika, Ruslan I et al. (2011) The Bcl-2 gene polymorphism rs956572AA increases inositol 1,4,5-trisphosphate receptor-mediated endoplasmic reticulum calcium release in subjects with bipolar disorder. Biol Psychiatry 69:344-52
Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) Genome-wide association study identifies five new schizophrenia loci. Nat Genet 43:969-76
Middleton, Frank A; Pato, Carlos N; Gentile, Karen L et al. (2005) Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches. Am J Med Genet B Neuropsychiatr Genet 136B:12-25
Pato, Carlos N; Middleton, Frank A; Gentile, Karen L et al. (2005) Genetic linkage of bipolar disorder to chromosome 6q22 is a consistent finding in Portuguese subpopulations and may generalize to broader populations. Am J Med Genet B Neuropsychiatr Genet 134B:119-21
Sklar, P; Pato, M T; Kirby, A et al. (2004) Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis. Mol Psychiatry 9:213-8
Xu, J; Pato, M T; Torre, C D et al. (2001) Evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. Am J Med Genet 105:669-74

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