It is proposed to study 90 sib-pairs with the disorder.
Specific aims are: (1) to clinically assess a pedigree sample having adequate power to detect genes for schizophrenia; (2) to conduct a genome scan to find such loci; and (3) to transmit all data to the NIMH designated cell repository and data management centers. The goals will be attained by achieving the following: (1) from Taiwan and China, 900 Han Chinese sib- pairs having DSM-IV schizophrenia will be collected. (2) The investigators will examine all family members using the Diagnostic Interview for Genetic Studies and the Family Interview for Genetic Studies. The PI participated in the development and field testing of these interviews and has an already established training program for their use. They have been translated into Mandarin by the Taiwanese investigators, who have used them in prior studies. (3) Blood samples will be sent to the NIMH designated cell repository for creation of lymphoblastoid cell lines. (4) Clinical data will be entered using the database software created for the NIMH Human Genetics Initiative. Data will be vetted and sent to the NIMH designated data management center. (5) The investigators will complete a genome scan using 450 markers spaced at an average of 10 cM intervals using markers that have been optimized for use in the Han Chinese population. The scan will be completed with no cost to the NIMH through an agreement with Millenium Pharmaceuticals, a biotechnology company in the Boston area that the PI has worked with on a prior genetic linkage study of schizophrenia. All genetic analyses will be approved by the consultant, Eric Lander, Ph.D. (6) all clinical data will be made available to the scientific community by the end of the funding period. All genotypes will be available on year after they are created but no later than a year after the funding period. This project is feasible because: (1) The PI has already coordinated one multi-site genetic linkage study of schizophrenia and has participated in a second. (2) The investigators have a longstanding relationship with the Taiwanese collaborators and an effective, albeit, more recent working relationship with the Chinese collaborator. (3) The investigators have conservatively estimated that each site has access to more than enough available families having two schizophrenic siblings. (4) The PI's Harvard team has had prior experience collaborating on genotyping and linkage analysis projects with Millennium Pharmaceuticals. This, and Millennium's prior genotyping experience shows that the genotyping phase of the work is feasible.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH059624-03
Application #
6186065
Study Section
Special Emphasis Panel (ZRG2-MGN (01))
Program Officer
Moldin, Steven Owen
Project Start
1998-09-30
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
3
Fiscal Year
2000
Total Cost
$838,764
Indirect Cost
Name
Massachusetts Mental Health Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
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Wang, S H; Liu, C M; Hwu, H G et al. (2015) Association of older paternal age with earlier onset among co-affected schizophrenia sib-pairs. Psychol Med 45:2205-13
Lin, Sheng-Hsiang; Liu, Chih-Min; Hwang, Tzung-Jeng et al. (2013) Performance on the Wisconsin Card Sorting Test in families of schizophrenia patients with different familial loadings. Schizophr Bull 39:537-46
Lien, Yin-Ju; Huang, Sih-Syuan; Liu, Chih-Min et al. (2013) A genome-wide quantitative linkage scan of niacin skin flush response in families with schizophrenia. Schizophr Bull 39:68-76
Chen, Wei J (2013) Taiwan Schizophrenia Linkage Study: lessons learned from endophenotype-based genome-wide linkage scans and perspective. Am J Med Genet B Neuropsychiatr Genet 162B:636-47
Chien, Yi-Ling; Hwu, Hai-Gwo; Fann, Cathy S-J et al. (2013) DRD2 haplotype associated with negative symptoms and sustained attention deficits in Han Chinese with schizophrenia in Taiwan. J Hum Genet 58:229-32
Yang, Hsin-Chou; Liu, Chih-Min; Liu, Yu-Li et al. (2013) The DAO gene is associated with schizophrenia and interacts with other genes in the Taiwan Han Chinese population. PLoS One 8:e60099
Lien, Yin-Ju; Hsiao, Po-Chang; Liu, Chih-Min et al. (2011) A genome-wide linkage scan for distinct subsets of schizophrenia characterized by age at onset and neurocognitive deficits. PLoS One 6:e24103
Liu, Chih-Min; Fann, Cathy S-J; Chen, Chien-Yu et al. (2011) ANXA7, PPP3CB, DNAJC9, and ZMYND17 genes at chromosome 10q22 associated with the subgroup of schizophrenia with deficits in attention and executive function. Biol Psychiatry 70:51-8
Tsuang, Hui-Chun; Liu, Chih-Min; Hwang, Tzung J et al. (2011) Handedness and schizotypy in non-psychotic relatives of patients with schizophrenia. Laterality 16:690-706

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