A non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6, is associated with heroin addiction

Dysregulation of the stress response is implicated in drug addiction; therefore, polymorphisms in stress-related genes may be involved in this disease. An analysis was performed to identify associations between variants in 11 stress-related genes, selected a priori, and heroin addiction. Two discove...

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Bibliographic Details
Published in:PloS one Vol. 13; no. 6; p. e0199951
Main Authors: Levran, Orna, Correa da Rosa, Joel, Randesi, Matthew, Rotrosen, John, Adelson, Miriam, Kreek, Mary Jeanne
Format: Journal Article
Language:English
Published: United States Public Library of Science 28.06.2018
Public Library of Science (PLoS)
Subjects:
Addictions
Adelson, Sheldon
Alcohol
Alcoholic beverages
Anxiety
Bioinformatics
Biology
Biology and life sciences
Care and treatment
Development and progression
Drug abuse
Drug addiction
Filtration
Gene expression
Genes
Genetic aspects
Genomes
Health aspects
Heroin
Heroin habit
Laboratories
Medicine and Health Sciences
Methadone
Minority & ethnic groups
Narcotics
Non-coding RNA
Permutations
Physical Sciences
Pituitary
Post traumatic stress disorder
Posttraumatic stress disorder
Principal components analysis
Psychiatry
Quantitative trait loci
Ribonucleic acid
RNA
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Social Sciences
Stress response
Stresses
Studies
Substance abuse treatment
New York
United States > US
Las Vegas Nevada
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Dysregulation of the stress response is implicated in drug addiction; therefore, polymorphisms in stress-related genes may be involved in this disease. An analysis was performed to identify associations between variants in 11 stress-related genes, selected a priori, and heroin addiction. Two discovery samples of American subjects of European descent (EA, n = 601) and of African Americans (AA, n = 400) were analyzed separately. Ancestry was verified by principal component analysis. Final sets of 414 (EA) and 562 (AA) variants were analyzed after filtering of 846 high-quality variants. The main result was an association of a non-coding SNP rs255105 in the CRH (CRF) receptor 2 gene (CRHR2), in the discovery EA sample (Pnominal = .00006; OR = 2.1; 95% CI 1.4-3.1). The association signal remained significant after permutation-based multiple testing correction. The result was corroborated by an independent EA case sample (n = 364). Bioinformatics analysis revealed that SNP rs255105 is associated with the expression of a downstream long intergenic non-coding RNA (lincRNA) gene AC005154.6. AC005154.6 is highly expressed in the pituitary but its functions are unknown. LincRNAs have been previously associated with adaptive behavior, PTSD, and alcohol addiction. Further studies are warranted to corroborate the association results and to assess the potential relevance of this lincRNA to addiction and other stress-related disorders.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0199951