Molecular genetic techniques have been developing rapidly, as have the statistical methods to draw the most information from the new types of results. In human genetics, however, developments on the phenotype side have been less dramatic. The research goal of this proposal is to partially redress that imbalance through the development and application of new methods for the genetic analysis of complex traits in the context of career development for the candidate, Dr. Steven Buyske. The research plan comprises three parts. First, Dr. Buyske will perform secondary analyses of the data collected by the Collaborative Studies on Genetics of Alcoholism, focusing on phenotype definitions involving neuropsychological traits, successful smoking cessation, and successful treatment outcomes for alcohol-dependent subjects, as well as the new methodological approaches developed in this proposal. Second, he will develop a fast, regression-based method for testing genetic linkage of multivariate quantitative traits. Such a method allows several correlated traits to be examined simultaneously. Third, he will develop a novel method for clustering individual diagnostic items to create synthetic phenotypes with a simpler genetic structure. These phenotypes might lack apparent clinical significance yet might bear a closer relationship to the underlying genetic structure, and so would be easier to map. Dr. Buyske will have Robert Pandina, Susan Hodge, David Greenberg, and Linda Brzustowicz as mentors. The training components of this proposal will include coursework in statistical genetics, genetics, alcohol and addiction studies, and the ethical conduct of research, as well as intensive training workshops and consultations. Support through this award will enable Dr. Buyske to develop a unique area of expertise within statistical genetics and develop into an independent investigator capable of conducting important quantitative biomedical research.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Mentored Quantitative Research Career Development Award (K25)
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Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Ren, Zhaoxia
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Rutgers University
Biostatistics & Other Math Sci
Schools of Arts and Sciences
New Brunswick
United States
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Brzustowicz, Linda M; Moreau, Michael P; Bruse, Shannon E et al. (2016) Reply to: Reproducibility and Visual Inspection of Data. Biol Psychiatry 80:e37-8
Moreau, Michael P; Bruse, Shannon E; David-Rus, Richard et al. (2011) Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder. Biol Psychiatry 69:188-93
Hadzimichalis, Norell M; Previtera, Michelle L; Moreau, Michael P et al. (2010) NOS1AP protein levels are altered in BA46 and cerebellum of patients with schizophrenia. Schizophr Res 124:248-50
Johnson, William G; Buyske, Steven; Mars, Audrey E et al. (2009) HLA-DR4 as a risk allele for autism acting in mothers of probands possibly during pregnancy. Arch Pediatr Adolesc Med 163:542-6
Wratten, Naomi S; Memoli, Holly; Huang, Yungui et al. (2009) Identification of a schizophrenia-associated functional noncoding variant in NOS1AP. Am J Psychiatry 166:434-41
Buyske, Steven (2008) Maternal genotype effects can alias case genotype effects in case-control studies. Eur J Hum Genet 16:783-5
Williams, Tanishia A; Mars, Audrey E; Buyske, Steven G et al. (2007) Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype. Arch Pediatr Adolesc Med 161:356-61
Matise, Tara C; Chen, Fang; Chen, Wenwei et al. (2007) A second-generation combined linkage physical map of the human genome. Genome Res 17:1783-6
Jean, Smith; Kasinathan, Chinnaswamy; Buyske, Steven et al. (2006) Ethanol decreases rat hepatic arylsulfatase A activity levels. Alcohol Clin Exp Res 30:1950-5
Buyske, Steven; Bates, Marsha E; Gharani, Neda et al. (2006) Cognitive traits link to human chromosomal regions. Behav Genet 36:65-76

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