Dataset Information

Susceptibility loci for heroin and cocaine addiction in the serotonergic and adrenergic pathways in populations of different ancestry.

ABSTRACT: Drug addiction is influenced by genetic factors.To determine if genetic variants in the serotonergic and adrenergic pathways are associated with heroin and/or cocaine addiction.The study examined 140 polymorphisms in 19 genes in 1855 subjects with predominantly European or African ancestries.A total of 38 polymorphisms (13 genes) showed nominal associations, including novel associations in S100A10 (p11) and SLC18A2 (VMAT2). The association of HTR3B SNP rs11606194 with heroin addiction in the European ancestry subgroup remained significant after correction for multiple testing (p(corrected) = 0.04).The study strengthens our previous findings of association of polymorphisms in HTR3A, HTR3B and ADRA1A. The study suggests partial overlap in genetic susceptibility between populations of different ancestry and between heroin and cocaine addiction.

SUBMITTER: Levran O

PROVIDER: S-EPMC4896084 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Susceptibility loci for heroin and cocaine addiction in the serotonergic and adrenergic pathways in populations of different ancestry.

Levran Orna O Peles Einat E Randesi Matthew M Correa da Rosa Joel J Ott Jurg J Rotrosen John J Adelson Miriam M Kreek Mary Jeanne MJ

Pharmacogenomics 20150731 12

<h4>Background</h4>Drug addiction is influenced by genetic factors.<h4>Aim</h4>To determine if genetic variants in the serotonergic and adrenergic pathways are associated with heroin and/or cocaine addiction.<h4>Subjects & methods</h4>The study examined 140 polymorphisms in 19 genes in 1855 subjects with predominantly European or African ancestries.<h4>Results</h4>A total of 38 polymorphisms (13 genes) showed nominal associations, including novel associations in S100A10 (p11) and SLC18A2 (VMAT2) ...[more]

PMID: 26227246

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Project description:Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, is a complex disease. The risk of developing active TB is in part determined by host genetic factors. Most genetic studies investigating TB susceptibility fail to replicate association signals particularly across diverse populations. South African populations arose because of multi-wave genetic admixture from the indigenous KhoeSan, Bantu-speaking Africans, Europeans, Southeast Asian-and East Asian populations. This has led to complex genetic admixture with heterogenous patterns of linkage disequilibrium and associated traits. As a result, precise estimation of both global and local ancestry is required to prevent both false positive and false-negative associations. Here, 820 individuals from South Africa were genotyped on the SNP-dense Illumina Multi-Ethnic Genotyping Array (∼1.7M SNPs) followed by local and global ancestry inference using RFMix. Local ancestry adjusted allelic association (LAAA) models were utilized owing to the extensive genetic heterogeneity present in this population. Hence, an interaction term, comprising the identification of the minor allele that corresponds to the ancestry present at the specific locus under investigation, was included as a covariate. One SNP (rs28647531) located on chromosome 4q22 was significantly associated with TB susceptibility and displayed a SNP minor allelic effect (G allele, frequency = 0.204) whilst correcting for local ancestry for Bantu-speaking African ancestry (p-value = 5.518 × 10-7; OR = 3.065; SE = 0.224). Although no other variants passed the significant threshold, clear differences were observed between the lead variants identified for each ancestry. Furthermore, the LAAA model robustly captured the source of association signals in multi-way admixed individuals from South Africa and allowed the identification of ancestry-specific disease risk alleles associated with TB susceptibility that have previously been missed.

Dataset Information

Susceptibility loci for heroin and cocaine addiction in the serotonergic and adrenergic pathways in populations of different ancestry.

Publications

Susceptibility loci for heroin and cocaine addiction in the serotonergic and adrenergic pathways in populations of different ancestry.

Similar Datasets

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