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 gene loci in contributing to human individual differences in drug abuse vulnerability and in individual differences in related phenotypes. We completed validation of GWA approaces using 1M SNP arrays and published updated reports of convergence of the increasingly-dense whole genome association genome scans for vulnerability to heavy use of/dependence on at least one illegal addctive substance, as well an ancillary data from users of other substances. Re reported comparisons between nicotine dependent and control groups of NIH reserach volunteers and between substance dependent and control Europena-American samples from a community representative sample from the Epidemiologic Catchment Area study. These data provide substantial support for almost 100 gene loci as containing allelic variants that confer vulnerability to substance abuse in individuals of African-American, European-American and Asian genetic backgrounds. 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. 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.
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