Linkage-based analyses for addiction vulnerabilities would be expected to reproducibly identify many of the genes whose variants exerted major influences on human addiction vulnerability. However, existing linkage data for human dependence on alcohol, nicotine and a number of other substances fails to provide any highly-reproducible results that would support any major gene locus ([22–31] and references in [32]). These results add to the conclusion that no locus individually appears to contribute a large fraction of the vulnerability to dependence on any addictive substance. There is a caveat: these data come from subjects with largely European ethnic/racial backgrounds [22, 23, 70–84]. Nevertheless, as with many complex human disorders in which initial hopes for a tractable (eg oligogenic) underlying genetic architecture supported use of linkage approaches, the linkage peaks that are identified in each individual study may be more likely to arise on other bases when the underlying architecture is in fact polygenic. Apparent linkage signals identified in single studies might result from polygenic influences from several genes that each happen to lie near each other on human chromosomes or to be found on stochastic bases when there is no true major effect from any single gene variant, for example [85].
