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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