Linkage studies of schizophrenia are hampered by low recurrence risk and a non-Mendelian mode of transmission. Although schizophrenia itself is not highly penetrant, traits that are associated with schizophrenia and that occur at a higher rate in relatives of schizophrenics could serve as useful pointers to the gene(s) for schizophrenia in linkage analysis. Prominent among these associated traits are eye tracking dysfunction, thought disorder, craniofacial dysmorphology, and clinical signs and symptoms associated with the schizophrenia spectrum. The investigators propose to maximize discrimination among genotypes by mapping these more prevalent associated quantitative traits, rather than relying on an all-or-none disease phenotype. Because this strategy bases affectedness on traits that have a higher genetic signal than schizophrenia, the investigators expect that it will increase the power of linkage analysis. The investigators will use both nonparametric and model-dependent methods to test for linkage in a sample comprising 160-208 sibling pair combinations. They will include recent modifications of the Haseman-Elston method as well as lod score analysis. They will use discriminant functions as quantitative phenotypes. They will scan the entire genome for evidence of linkage to individual quantitative phenotypes and combinations of quantitative phenotypes by typing highly informative multi-allele markers, using a map of 10 cM or less. Robust statistical methods for evaluating the results of genomic scans will be developed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH049487-09
Application #
6499243
Study Section
Clinical Psychopathology Review Committee (CPP)
Program Officer
Moldin, Steven Owen
Project Start
1992-06-01
Project End
2005-01-31
Budget Start
2002-02-01
Budget End
2005-01-31
Support Year
9
Fiscal Year
2002
Total Cost
$272,541
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
City
Belmont
State
MA
Country
United States
Zip Code
02478
Morgan, Charity J; Coleman, Michael J; Ulgen, Ayse et al. (2017) Thought Disorder in Schizophrenia and Bipolar Disorder Probands, Their Relatives, and Nonpsychiatric Controls. Schizophr Bull 43:523-535
Deutsch, Curtis K; Levy, Deborah L; Price, Selya F R et al. (2015) Quantitative Measures of Craniofacial Dysmorphology in a Family Study of Schizophrenia and Bipolar Illness. Schizophr Bull 41:1309-16
Morgan, Charity J; Lenzenweger, Mark F; Rubin, Donald B et al. (2014) A hierarchical finite mixture model that accommodates zero-inflated counts, non-independence, and heterogeneity. Stat Med 33:2238-50
Coleman, Michael J; Titone, Debra; Krastoshevsky, Olga et al. (2010) Reinforcement ambiguity and novelty do not account for transitive inference deficits in schizophrenia. Schizophr Bull 36:1187-200
Krause, Verena; Krastoshevsky, Olga; Coleman, Michael J et al. (2010) Tailoring the definition of the clinical schizophrenia phenotype in linkage studies. Schizophr Res 116:133-42
Coleman, Michael J; Cestnick, Laurie; Krastoshevsky, Olga et al. (2009) Schizophrenia patients show deficits in shifts of attention to different levels of global-local stimuli: evidence for magnocellular dysfunction. Schizophr Bull 35:1108-16
Chen, Yue; Grossman, Emily D; Bidwell, L Cinnamon et al. (2008) Differential activation patterns of occipital and prefrontal cortices during motion processing: evidence from normal and schizophrenic brains. Cogn Affect Behav Neurosci 8:293-303
Ulgen, Ayse; Yoo, Yun Joo; Gordon, Derek et al. (2004) Percentiles of the null distribution of 2 maximum lod score tests. Hum Hered 57:39-48
Levy, Deborah L; O'Driscoll, Gillian; Matthysse, Steven et al. (2004) Antisaccade performance in biological relatives of schizophrenia patients: a meta-analysis. Schizophr Res 71:113-25
Titone, Debra; Ditman, Tali; Holzman, Philip S et al. (2004) Transitive inference in schizophrenia: impairments in relational memory organization. Schizophr Res 68:235-47

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