Renato Polimanti1,2, Can Yang1,3, Hongyu Zhao3,4, Joel Gelernter1,2,4,5. 1. Department of Psychiatry, Yale University School of Medicine, VA CT 116A2, 950 Campbell Avenue, West Haven, CT 06516, USA. 2. VA CT Healthcare Center, West Haven, CT 06516, USA. 3. Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520-8034, USA. 4. Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA. 5. Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Abstract
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.
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.
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