Several alcohol dependence risk loci are now known, and specific candidate genes have been identified as potentially important for the component projects in the center. The major function of the Genetics Core will be to support genotyping for each of the projects (including pilot projects) involving human subjects, for the purpose of identifying genotype/phenotype correlations. A minimal set of relevant loci will be studied in all subjects. This gene set will be adjusted during the span of the center to incorporate newly-identified biological pathways, and new candidates identified by other methods (e.g., genomewide association studies [GWAS] taking place in our research group and elsewhere). The goals of the clinical components of the Center require study of ethnically heterogeneous populations, but study of stratified samples that differ in allele frequency and phenotype for candidate loci of interest can create artifactual association. We will therefore apply structured association methodology to measure and if necessary statistically correct for the effects of population stratification. Genetics Core investigators will advise Center investigators for issues related to genetics studies. Specifically, this will include (a) consultation on genetics-related human subjects issues;(b) consultation regarding study design (which may include preselection of subjects by genotype in some cases, as well as selection of genes and specific markers for study);(c) statistical analyses (including implementation of analyses results involving ancestry-informative markers);and (d) consultation to aid in interpretation of results.
Genetic factors influence risk for alcohol dependence per se, and also aspects of phenotype related to diagnosis of alcohol dependence. It is critically important to understand specific genes that influence these phenotypes, diagnostic and intermediate, and it is the goal of this core to aid in that understanding.
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|Wang, Qian; Polimanti, Renato; Kranzler, Henry R et al. (2017) Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions. Hum Genet 136:75-83|
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|Polimanti, Renato; Gelernter, Joel (2017) ADH1B: From alcoholism, natural selection, and cancer to the human phenome. Am J Med Genet B Neuropsychiatr Genet :|
|Polimanti, Renato; Jensen, Kevin P; Gelernter, Joel (2017) Phenome-wide association study for CYP2A6 alleles: rs113288603 is associated with hearing loss symptoms in elderly smokers. Sci Rep 7:1034|
|Polimanti, Renato; Agrawal, Arpana; Gelernter, Joel (2017) Schizophrenia and substance use comorbidity: a genome-wide perspective. Genome Med 9:25|
|Polimanti, Renato; Gelernter, Joel; Stein, Dan J (2017) Genetically determined schizophrenia is not associated with impaired glucose homeostasis. Schizophr Res :|
|Polimanti, Renato; Wang, Qian; Meda, Shashwath A et al. (2017) The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk Gene. Neuropsychopharmacology 42:598-605|
|Polimanti, Renato; Meda, Shashwath A; Pearlson, Godfrey D et al. (2017) S100A10 identified in a genome-wide gene × cannabis dependence interaction analysis of risky sexual behaviours. J Psychiatry Neurosci 42:252-261|
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