Dissecting ancestry genomic background in substance dependence genome-wide association studies.

AIMS To understand the role of ancestral genomic background in substance dependence (SD) genome-wide association studies (GWAS), we analyzed population diversity at genetic loci associated with SD traits and evaluated its effect on GWAS outcomes. MATERIALS & METHODS We investigated 24 genes with variants associated with SD by GWAS; and 82 loci with putative subordinate roles with respect to SD-associated genes. RESULTS We observed high ancestry-related frequency differences in common functional alleles in GWAS relevant genes and their interactive partners. Common functional alleles with high frequency differences demonstrated significant effects on the GWAS outcomes. CONCLUSION Population differences in SD GWAS outcomes seem not to be influenced by general variation across the genome, but by ancestry-related local haplotype structures at SD-associated loci.