MIRECC / CoE
VISN 1 New England MIRECC Current Human Neurobiological Research
Genome-wide Association Studies of Alcohol, Opioid, and Nicotine Dependence
Contact: Joel Gelernter, M.D. (Joel.Gelernter@va.gov)
Gene discovery can lead to risk prediction and identification of new biological targets for drug therapies. Genome-wide association studies may be used to identify genes influencing risk for the disorders under study without any prior knowledge of their physiology. Thus, they are well suited to discover novel mechanisms. We have had multiple projects funded to permit us to study a set of substance dependence traits in both European-American and African-American individuals. We hope that this work will lead to gene discovery which can lead to risk prediction and identification of new biological targets for drug therapies.
Publications: (1) Han, S., Yang, B-Z., Kranzler, H.R., Oslin, D., Anton, R., & Gelernter. J. (2011). Association of CHRNA4 polymorphisms with smoking behavior in two populations. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 156(4), 421-429; (2) Herman, A.I., Jatlow, P.I., Gelernter, J., Listman, J.B., & Sofuoglu, M. (2013). COMT Val158MET modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers. Pharmacogenomics, 13(6), 490-497; (3) Li, D., Zhao, H., & Gelernter, J. (2011). Strong association of the alcohol dehydrogenase 1B gene (ADH1B) with alcohol dependence and alcohol-induced medical diseases. Biological Psychiatry, 70(6), 504-512; (4) Li, D., Zhao, H., & Gelernter, J. (2012). Further clarification of the contribution of the ADH1C gene to vulnerability of alcoholism and selected liver diseases. Human Genetics, 131(8), 1361-1374; (5) Xie, P., Kranzler, H.R., Farrer, L., & Gelernter, J. (2012). Serotonin transporter 5-HTTLPR genotype moderates the effects of childhood adversity on post-traumatic stress disorder risk: A replication study. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 159B(6), 644-652; (6) Xie, P., Kranzler, H.R., Krauthammer, M., Cosgrove, K.P., Oslin, D., Anton, R.F., Farrer, L.A., Picciotto, M.R., Krystal, J.H., Zhao, H., & Gelernter, J. (2011). Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence. Biological Psychiatry, 70(6), 528-536; (7) Xie, P., Kranzler, H.R., Zhang, H., Oslin, D., Anton, R.F., Farrer, L.A., & Gelernter, J. (2012). Childhood adversity increases risk for nicotine dependence and interacts with alpha-5 nicotinic acetylcholine receptor genotype specifically in males. Neuropsychopharmacology, 37, 669-676; (8) Herman, A.I., Jatlow, P.I., Gelernter, J., Listman, J.B., & Sofuoglu, M. (2013). COMT Val158MET modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers. Pharmacogenomics, 13(6), 490-497; (9) Arias, A.J., Gelernter, J., Gueorguieva, R., Ralevski, E., & Petrakis, I. (2014). Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed Veterans. The American Journal on Addictions, 23(3), 288-293; and (10) Jensen, K.P., Herman, A.I., Morean, M.E., Kranzler, H.R., Gelernter, J., & Sofuoglu, M. (2014). FKBP5 variation is associated with the acute and chronic effects of nicotine. Pharmacogenomics Journal, 15(4), 340-346.
