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

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

Polimanti R1,2, Yang C1,3, Zhao H3,4, Gelernter J1,2,4,5.

Author information

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.

KEYWORDS:

African–Americans; European–Americans; ethnicity; substance dependence

PMID:
26267224
PMCID:
PMC4632979
DOI:
10.2217/pgs.15.91
[Indexed for MEDLINE]
Free PMC Article
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