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Drug Dependence
Oscar M. Harari, Ph.D.
Xin Zhou, Ph.D.
Sean D. Kristjansson, Ph.D.
Ruth Huang Miller, Ph.D.
Wei (Will) Yang, Ph.D.
Bo Zhang, Ph.D.
Sumithra Sankararaman
Ni Huang, Ph.D.

Oscar M. Harari, Ph.D. 


 Oscar M. Harari, Ph.D.    

   Year in Program:   Completed, January 2013

Primary Mentor:

   Alison M. Goate, DPhil
   Professor of Genetics and Psychiatry
   Division of Biology and Biomedical Sciences
   Washington University School of Medicine


  Symposium Presentation 
  Power Point Link 
(viewable as pdf) 

Project Description

Dr. Oscar Harari is a computer scientist from Argentina (Ph.D. Thesis: Predicting prokaryotic and eukaryotic gene networks by fusing domain knowledge with conceptual clustering algorithms, University of Granada, Spain), who is currently mentored by Drs. Zhang (Dept. of Computer Science) and Alison Goate (molecular research with a focus on addiction genetics; Dept of Psychiatry) on the development and implementation of novel computational algorithms for reweighting genome-wide association study data using evolutionary and other biological considerations (i.e., computational biology: program development).

He has two projects; 1) the formulation of hypotheses that explain the biological relevance of significant signals found in GWAS, by using repository data and the employment of existing bioinformatics tools; and 2) the development and the application of a new computational method for evaluating and identifying overrepresented pathways and terms of gene-ontology related to nicotine addiction in GWAS studies.

He is extending a computational method called ALIGATOR (Holmans P, et al., 2009), to allow the specification of which regions of the chromosome/gene should be analyzed. This extension would enable the analysis of the different terms that are identified when the signals originate only in the exons, and when distinct regions (i.e., 5’ UTR; introns; 3’UTR; promoters; flanking regions; and haplotypes) are incorporated into the analysis of nicotine addiction GWAS data.  Dr. Harari is initially applying these methods to GWAS data from the Madden and Bierut tobacco genetics studies, i.e., nicotine addiction. 


Program Presentations

Harari O, Madden PAF, Bierut LJ, Goate AM, NAG and COGEND collaborators, Gene ontology analysis of Genome-wide Association Studies for Nicotine Dependence.  Oral presentation: New Statistical Methods for Genetic Research on Addiction. Symposium: 41st Annual Meeting of the Behavior Genetics Association (BGA), Newport, RI, June 2011.

Harari O, Madden PAF, Bierut LJ, Goate AM, NAG and COGEND collaborators. Poster presentation: Pathway-based approach to analyze GWAS for Nicotine Dependence. Department of Psychiatry Fellows Poster Session, Washington University Medical School, St. Louis, MO, November 2010.

Harari O, Wang JC, Bierut LJ, Madden PAF, Goate AM, NAG and SAGE collaborators. Poster presentation: Pathway analysis approach for interpreting nicotine dependence GWAS. 12th International Congress of Human Genetics/American Society of Human Genetics 61st Annual Meeting, Montreal, QC, Canada, Oct 2011.

Harari O, Goate AM and GENEVA Alcohol Consumption Working Group. Pathway analysis of the geneva alcohol consumption GWAS meta-analysis. Poster presentation. The American Society of Human Genetics 62nd  Annual Meeting, San Francisco, CA, USA, Oct 2012.

Harari O, Goate AM. Pathway Analysis for Smoking Quantity.  Oral Presentation.  National Institute of Drug Abuse – Genetics Consortium Winter Meeting, Washington, DC, USA, Dec 2012.

O. Harari. (Oral Presentation): Pathway analysis for smoking quantity. R25 Fellowship Symposium: Statistical and Computational Innovation in Addiction Genetics, Washington University School of Medicine, Saint Louis, MO, December 2013.


Program Publications

Harari O, Cruchaga C, Kauwe JSK, Bales K, Pickering EH, Bertelsen S, the Alzheimer’s Disease Neuroimaging Initiative, Fagan AM, Holtzman DM, Morris JC, Goate AM. Ptau-Aβ42 Ratio as a continuous trait for biomarker discovery for early stage Alzheimer’s disease in multiplex immunoassay panels of cerebrospinal fluid. Biological Psychiatry. In press.

Cruchaga C, Karch CM, Jin SC, Benitez BA, Guerreiro R, Harari O, et al. Rare coding variants in phospholipase D3 (PLD3) confer risk for Alzheimer’s disease. Nature. In press.

Wang JC, Spiegel N, Bertelsen S, Le N, McKenna N, Budde JP, Harari O, Kapoor M, Brooks A, Hancock D, Tischfield J, Foroud T, Bierut LJ, Steinbach JH, Edenberg HJ, Traynor BJ, Goate AM. Cis-regulatory variants affect CHRNA5 mRNA expression in populations of African and European ancestry. PLoS ONE. In press.

Kapoor M, Wang JC, Wetherill L, Le N, Bertelsen S, Hinrichs AL, Budde J, Agrawal A, Bucholz K, Dick D, Harari O, Hesselbrock V, Kramer J, Nurnberger JI Jr, Rice J, Saccone N, Schuckit M, Tischfield J, Porjesz B, Edenberg HJ, Bierut L, Foroud T, Goate A. A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks. Hum Genet. 2013 Oct; 132:1141-51. Epub 2013 Jun 7. PMID: 23743675. PMC3776011.

Cruchaga C, Kauwe JS, Harari O, Jin SC, Cai Y, Karch CM, Benitez BA, et al. GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease. Neuron. 2013 Apr; 78:256-268. PMID: 23562540. PMC3664945.

Bloom AJ, Harari O, Martinez M, Zhang X, McDonald SA, Murphy SE, et al. A compensatory effect upon splicing results in normal function of the CYP2A6*14 allele. Pharmacogenet Genomics 2013; 23: 107–116. doi: 10.1097/FPC.0b013e32835caf7d. PMID: 23292114.

Harari O, J-C. Wang, K. Bucholz, H. J. Edenberg, A. Heath, N. G. Martin, M. L. Pergadia, G. Montgomery, A. Schrage, L. J. Bierut, P. F. Madden, A. M. Goate. Pathway analysis of smoking quantity in multiple GWAS identifies cholinergic and sensory pathways. PLoS ONE. 2012 Dec; e50913. PMID: 23227220. PMC3515482.

Wang JC, Foroud T, Hinrichs AL, Le NX, Bertelsen S, Budde JP, Harari O, et al. A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. Mol Psychiatry. Oct. 2012. doi: 10.1038/mp.2012.143.  PMID: 23089632. [Epub ahead of print]

Bloom AJ, O Harari, Martinez M, Madden PAF, Martin NG, Montgomery GW, et al. Use of a predictive model derived from in vivo endophenotype measurements to demonstrate associations with a complex locus, CYP2A6. Human Molecular Genetics 2012 Jul. 1; 21: 3050–62. PMID: 22451501. PMC3373237. 

Harari O, Park SY, Huang H, Groisman EA, Zwir I. Defining the plasticity of transcription factor binding sites by Deconstructing DNA consensus sequences: the PhoP-binding sites among gamma/enterobacteria. PLoS Comput Biol. 2010 Jul 22; 6(7):e1000862. PMID: 20661307. PMC2908699.