subsequently. As discussed in Drgon et al. (2011), the definition of “replication” in GWAS for major gene effects that involve the same allele is relatively straightforward, but this is not the circumstance for phenotypes that have a polygenic genetic architecture, high allelic heterogeneity, and high locus heterogeneity, and when the arrangement of linkage disequilibria differs across populations or samples. Thus, “replication” should be defined based on identification of the same chromosomal regions; which effectively means regions of individual genes defined by high linkage disequilibrium once the marker density in GWAS is sufficiently dense. Based on these criteria, there was substantial replication of results across these studies despite their differences, which produced a substantial overlap in the genes identified, as discussed in more detail below. Furthermore, comparison of the results of GWAS and murine quantitative trait locus studies for ethanol, methamphetamine and barbiturates indicates substantial overlap as well (G. R. Uhl, Drgon, Johnson, Fatusin, et al., 2008).
