biological mechanisms that may be associated with REX scores, two patterns stand out. The first pattern relates to steroid response or metabolism. We identified a GWS association mapped to a well-known 900 kb inversion region (MAF ~0.2 in Europeans)11 that includes CRHR1, although in EAs the lead SNP mapped at KANSL1. In general, fine-mapping risk loci by statistical methods is difficult in regions of high LD. The inversion is much less common in Africans11,12 so meta-analysis between EAs and AAs would have the potential to narrow the associated region greatly, assuming a meaningful association is present in the latter population also. And indeed, on transpopulation meta-analysis, the statistical significance increased by about an order of magnitude (to rs174409 p=3.6×10−11) with the lead SNP now mapped to CHRH1, a locus with considerable prior support on the basis of known biology.13 Thus, even though our AA sample was too small for locus identification when taken individually, transpopulation meta-analysis was very valuable because of the differences not just in local LD but in larger-scale genomic structure (Figure S6). CRHR1 also emerged as one of top genes in the gene-based genomewide analysis using MAGMA; and it was also replicated in the UKB cohort. CRHR1
