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


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.


CONCLUSIONS
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.
Department of Psychiatry, Yale University School of Medicine, VA CT 116A2, 950 Campbell Avenue, West Haven, CT 06516, USA.|VA CT Healthcare Center, West Haven, CT 06516, USA.
Renato
R
Polimanti
Department of Psychiatry, Yale University School of Medicine, VA CT 116A2, 950 Campbell Avenue, West Haven, CT 06516, USA.|Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520-8034, USA.
Can
C
Yang
Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520-8034, USA.|Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Hongyu
H
Zhao
Department of Psychiatry, Yale University School of Medicine, VA CT 116A2, 950 Campbell Avenue, West Haven, CT 06516, USA.|VA CT Healthcare Center, West Haven, CT 06516, USA.|Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.|Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Joel
J
Gelernter
D001741:Black or African American; D000437:Alcoholism / Q000235:genetics; D000465:Algorithms; D000483:Alleles; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D058977:Molecular Sequence Annotation; D009293:Opioid-Related Disorders / Q000235:genetics; D019966:Substance-Related Disorders / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics; D044465:White People
African–Americans; European–Americans; ethnicity; substance dependence