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

Pharmacogenomics. 2015;16(13):1487-98. doi: 10.2217/pgs.15.91. Epub 2015 Aug 12.

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.

Keywords: African–Americans; European–Americans; ethnicity; substance dependence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alcoholism / genetics
  • Algorithms
  • Alleles
  • Black or African American
  • Gene Frequency
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study*
  • Haplotypes
  • Humans
  • Molecular Sequence Annotation
  • Opioid-Related Disorders / genetics
  • Substance-Related Disorders / genetics*
  • Tobacco Use Disorder / genetics
  • White People

Associated data

  • dbGaP/PHS000092.V1.P1