This variant has many orders of magnitude greater support for association than the next-best-supported independent region on chromosome 17, lead SNP rs77804065, which maps to CRHR1, observed p=1.5×10−12 in EUR. CHRH1 variants were previously implicated in candidate gene studies of alcohol use phenotypes(42, 43) and in an animal study regarding sensitivity to relapse into alcohol seeking induced by environmental stress (44). This GWS association signal maps to a well-known 900 kb inversion region (45) containing numerous other genes, some of which could also be considered MaxAlc candidate loci. The inversion is much less common in Africans (45, 46) consistent with the complex evolutionary history at this locus (47), so meta-analysis between EUR and AFR could potentially narrow the associated region greatly, if there is association information in that population as well, even if non-significant taken only in AFR. Indeed, the transpopulation meta-analysis showed that statistical significance increased by over an order of magnitude (to 1.02×10−13) with improved evidence for localization of the lead SNP at CHRH1 (Figure 2c). A similar phenomenon has been observed in narrowing associated regions for schizophrenia
