This is an application for a 5-year Mentored Clinical Scientist Development Award (K08). The candidate has received training in human genetics and additional training in psychiatry. The goal for this award is to develop the candidate's skills in gene mapping of complex traits, such as psychiatric disorders, using symptom dimensions and neurophysiologically defined endophenotypes as traits. During the time of the award, the candidate will acquire knowledge in the application of newly developed statistical methods to address the problem of clinical heterogeneity in patient samples with psychotic disorders. Understanding the heterogeneity in these disorders is one of the major challenges in the attempt to identify underlying genetic mutations. Defining the differences in clinical symptoms and neurophysiologic functioning is therefore of utmost importance. Several recent findings suggest that this approach to gene identification is useful. The long-term aim of the candidate is to understand the cognitive, emotional, behavioral and neurophysiologic abnormalities of psychotic disorders, their overlaps and their differences and to link these to molecular abnormalities. This may, if successful, enhance the understanding of these disorders and improve diagnostics and treatment. The training goal will be reached using the following steps: 1. A combination of factor analysis and latent class analysis (factor mixture model) will be used to subgroup patients from the NIMH schizophrenia and bipolar genetics initiatives. 2. Linkage analysis and quantitative trait locus mapping will be performed on these so defined subgroups. 3. Experience in the use of endophenotypes for genetic studies will be obtained through participation in ongoing studies at UCLA. The Neuropsychiatric Institute at UCLA provides the ideal environment for this proposal. The mentorship of Dr. Nelson Freimer, Dr. Andrew Leuchter and Dr. Bengt Muthen, who are all experts in overlapping aspects of this proposal, will guarantee the success of the training, complemented by coursework and conferences.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08MH074057-05
Application #
7638624
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Chavez, Mark
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
5
Fiscal Year
2009
Total Cost
$163,620
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kerner, Berit (2015) Comorbid substance use disorders in schizophrenia: a latent class approach. Psychiatry Res 225:395-401
Kerner, Berit (2014) Genetics of bipolar disorder. Appl Clin Genet 7:33-42
Kerner, Berit; Rao, Aliz R; Christensen, Bryce et al. (2013) Rare Genomic Variants Link Bipolar Disorder with Anxiety Disorders to CREB-Regulated Intracellular Signaling Pathways. Front Psychiatry 4:154
Oetting, William S; Robinson, Peter N; Greenblatt, Marc S et al. (2013) Getting ready for the Human Phenome Project: the 2012 forum of the Human Variome Project. Hum Mutat 34:661-6
Lin, Chen Min; Sathirapongsasuti, Fah J; Kerner, Berit (2011) Propensity score analysis in the Genetic Analysis Workshop 17 simulated data set on independent individuals. BMC Proc 5 Suppl 9:S71
Kerner, Berit; Lambert, Christophe G; Muthén, Bengt O (2011) Genome-wide association study in bipolar patients stratified by co-morbidity. PLoS One 6:e28477
Kerner, Berit; North, Kari E; Fallin, M Daniele (2009) Use of longitudinal data in genetic studies in the genome-wide association studies era: summary of Group 14. Genet Epidemiol 33 Suppl 1:S93-8
Kerner, Berit; Jasinska, Anna J; DeYoung, Joseph et al. (2009) Polymorphisms in the GRIA1 gene region in psychotic bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 150B:24-32
Kerner, Berit; Muthén, Bengt O (2009) Growth mixture modelling in families of the Framingham Heart Study. BMC Proc 3 Suppl 7:S114
Kerner, Berit (2009) Glutamate Neurotransmission in Psychotic Disorders and Substance Abuse. Open Psychiatr J 3:1-8

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