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 reported results of GWA approaces using 1M SNP arrays, updating the remarkable 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 (while failing to identify results of reproducible """"""""genome wide"""""""" significance, as we have anticipated. We completed analyses of repsubstance dependent and control African-American samples from a community representative sample from the Prevention Study. Taken together, these data provide substantial support for many gene loci as containing allelic variants that confer vulnerability to substance abuse in individuals of African-American, European-American and Asian genetic backgrounds, as well as overlaps between these loci and those that may provide individual differences in responses to prevention interventions. 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, and in datasets from other laboratories that became available 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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