Schizophrenia is one of the world's major unsolved public health problems. It is a relatively common, chronic, debilitating disease of variable expression. Little is known about the causes of schizophrenia but there is convincing evidence that genetic factors play some role in the etiology of schizophrenia. However, the mechanism is not known. Most investigators believe schizophrenia is etiologically heterogeneous. The long term objective of this study is to identify the genes associated with susceptibility to this complex disease. This will be achieved through molecular genetic approaches. Linkage analysis and linkage disequilibrium studies using highly polymorphic microsatellite markers in a unique genetically homogeneous community (Ashkenazi Jews) will be conducted.
The specific aims of the proposal are as follows: 1) to recruit and evaluate a sample of 150 Ashkenazi Jewish patients who are diagnosed as having either schizophrenia or schizoaffective disorder (depressed type) and whose parents are willing to participate (trio panel). It is anticipated that 50 such trios will be identified prior to the beginning of this study, from other sources of funding so that the total trio sample will be comprised of 200 Ashkenazi Jewish patients and their parents. DNA will be isolated and lymphocytes will be isolated, frozen and stored; 2) to recruit and evaluate an independent sample of 100 Ashkenazi Jewish families with affected siblings and at least one parent willing to participate. Virus transformed lymphoblastoid cell lines from the affected siblings and their parents in the 100 sib-pair families will be obtained as well as DNA from direct extraction; 3) to genotype highly polymorphic microsatellite markers in regions of interest previously identified in other populations in both the trio sample and the sib-pair sample, as well as to complete genome-wide scans in both the trio sample and the sib-pair sample to detect new susceptibility loci; 4) to follow-up families to maintain current affected status; and 5) to make this unique clinical resource available to other investigators pursuing this goal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH057314-04
Application #
6363682
Study Section
Genome Study Section (GNM)
Program Officer
Moldin, Steven Owen
Project Start
1998-03-01
Project End
2004-02-29
Budget Start
2001-03-01
Budget End
2004-02-29
Support Year
4
Fiscal Year
2001
Total Cost
$639,698
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Pham, X; Song, G; Lao, S et al. (2016) The DPYSL2 gene connects mTOR and schizophrenia. Transl Psychiatry 6:e933
Goes, Fernando S; McGrath, John; Avramopoulos, Dimitrios et al. (2015) Genome-wide association study of schizophrenia in Ashkenazi Jews. Am J Med Genet B Neuropsychiatr Genet 168:649-59
Avramopoulos, Dimitrios; Pearce, Brad D; McGrath, John et al. (2015) Infection and inflammation in schizophrenia and bipolar disorder: a genome wide study for interactions with genetic variation. PLoS One 10:e0116696
Hatzimanolis, A; McGrath, J A; Wang, R et al. (2013) Multiple variants aggregate in the neuregulin signaling pathway in a subset of schizophrenia patients. Transl Psychiatry 3:e264
Li, Qing; Fallin, M Daniele; Louis, Thomas A et al. (2010) Detection of SNP-SNP interactions in trios of parents with schizophrenic children. Genet Epidemiol 34:396-406
Liu, Yaping; Chen, Pei-Lung; McGrath, John et al. (2010) Replication of an association of a common variant in the Reelin gene (RELN) with schizophrenia in Ashkenazi Jewish women. Psychiatr Genet 20:184-6
McGrath, John A; Avramopoulos, Dimitrios; Lasseter, Virginia K et al. (2009) Familiality of novel factorial dimensions of schizophrenia. Arch Gen Psychiatry 66:591-600
Chen, Pei-Lung; Avramopoulos, Dimitrios; Lasseter, Virginia K et al. (2009) Fine mapping on chromosome 10q22-q23 implicates Neuregulin 3 in schizophrenia. Am J Hum Genet 84:21-34
Fallin, M Daniele; Lasseter, Virginia K; Avramopoulos, Dimitrios et al. (2005) Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios. Am J Hum Genet 77:918-36
Mowry, B J; Holmans, P A; Pulver, A E et al. (2004) Multicenter linkage study of schizophrenia loci on chromosome 22q. Mol Psychiatry 9:784-95

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