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.
|DeLorenzo, Christine; DellaGioia, Nicole; Bloch, Michael et al. (2015) In vivo ketamine-induced changes in [¹¹C]ABP688 binding to metabotropic glutamate receptor subtype 5. Biol Psychiatry 77:266-75|
|Li, Dawei; Zhao, Hongyu; Kranzler, Henry R et al. (2015) Genome-wide association study of copy number variations (CNVs) with opioid dependence. Neuropsychopharmacology 40:1016-26|
|Xie, Pingxing; Kranzler, Henry R; Krystal, John H et al. (2014) Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence. Addict Biol 19:955-64|
|Barker, Jacqueline M; Taylor, Jane R (2014) Habitual alcohol seeking: modeling the transition from casual drinking to addiction. Neurosci Biobehav Rev 47:281-94|
|Steele, Vaughn R; Claus, Eric D; Aharoni, Eyal et al. (2014) A large scale (N=102) functional neuroimaging study of error processing in a Go/NoGo task. Behav Brain Res 268:127-38|
|Darcq, Emmanuel; Hamida, Sami Ben; Wu, Su et al. (2014) Inhibition of striatal-enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption. J Neurochem 129:1024-34|
|Yang, Can; Li, Cong; Kranzler, Henry R et al. (2014) Exploring the genetic architecture of alcohol dependence in African-Americans via analysis of a genomewide set of common variants. Hum Genet 133:617-24|
|Morean, Meghan E; DeMartini, Kelly S; Leeman, Robert F et al. (2014) Psychometrically improved, abbreviated versions of three classic measures of impulsivity and self-control. Psychol Assess 26:1003-20|
|Xu, Hongqin; Wang, Fan; Liu, Yawen et al. (2014) Sex-biased methylome and transcriptome in human prefrontal cortex. Hum Mol Genet 23:1260-70|
|Krystal, John H; State, Matthew W (2014) Psychiatric disorders: diagnosis to therapy. Cell 157:201-14|
Showing the most recent 10 out of 169 publications