Genetic Approaches To Characterizing Drug Responses And

National Institute On Drug Abuse

Investigators

Linked publications & trials

Abstract

Individual differences in drug abuse vulnerabilities among humans display genetic as well as environmental components. During this year, these investigators continued to explore roles of allelic variants at candidate gene loci in contributing to human individual differences in drug abuse vulnerability. We published updated reports of convergence of the increasingly-dense "whole genome association" genome scans to identifying previously-unanticipated gene loci conferring drug abuse vulnerabilities. We continued to make major advances in providing simulations and modeling for the power of genome-wide and focused association/linkage-disequilibrium based genome scanning, including developing novel models for the effect of genotype-based stratification on the power and costs of clinical trials for nicoting dependence. Work during this year provided replication and extension of identificaiton of candidate regions on several human chromosomes using high-density SNP-based linkage-disequilibrium based genome scanning, generating more than 4 billion person/genotypes. Data is consistent with the emerging models that genetic influences are polygenic, with few major gene influences. Several chromosomal regions previously nomninated by our studies have been replicated in new work completed during this year. Fine mapping studies have identified particular haplotypes at several gene loci that represent the strongest candidates for addiction vulnerability genes in humans. These studies point toward a role for individual differences in brain structures, as well as functions, in vulnerability to addictions and especial roles for genes encoding molecules that participate in "cell adhesion" mechanisms.