A 3' UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction.
3' Untranslated Regions
/ genetics
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Circadian Rhythm
/ genetics
Genetic Predisposition to Disease
Humans
Opioid-Related Disorders
/ genetics
Period Circadian Proteins
/ genetics
Polymorphism, Single Nucleotide
Quantitative Trait Loci
/ genetics
RNA, Long Noncoding
/ genetics
Receptors, Vasoactive Intestinal Peptide, Type II
/ genetics
Repressor Proteins
/ genetics
Reward
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
22
08
2019
accepted:
12
10
2019
entrez:
6
11
2019
pubmed:
7
11
2019
medline:
3
4
2020
Statut:
epublish
Résumé
There is a reciprocal relationship between the circadian and the reward systems. Polymorphisms in several circadian rhythm-related (clock) genes were associated with drug addiction. This study aims to search for associations between 895 variants in 39 circadian rhythm-related genes and opioid addiction (OUD). Genotyping was performed with the Smokescreen® array. Ancestry was verified by principal/MDS component analysis and the sample was limited to European Americans (EA) (OUD; n = 435, controls; n = 138). Nominally significant associations (p < 0.01) were detected for several variants in genes encoding vasoactive intestinal peptide receptor 2 (VIPR2), period circadian regulator 2 (PER2), casein kinase 1 epsilon (CSNK1E), and activator of transcription and developmental regulator (AUTS2), but no signal survived correction for multiple testing. There was intriguing association signal for the untranslated region (3' UTR) variant rs885863 in VIPR2, (p = .0065; OR = 0.51; 95% CI 0.31-0.51). The result was corroborated in an independent EA OUD sample (n = 398, p = 0.0036; for the combined samples). Notably, this SNP is an expression quantitative trait locus (cis-eQTL) for VIPR2 and a long intergenic non-coding RNA, lincRNA 689, in a tissue-specific manner, based on the Genotype-Tissue Expression (GTEx) project. Vasoactive intestinal peptide (VIP) is an important peptide of light-activated suprachiasmatic nucleus cells. It regulates diverse physiological processes including circadian rhythms, learning and memory, and stress response. This is the first report of an association of a VIPR2 variant and OUD. Additionally, analysis of combinations of single nucleotide polymorphisms (SNPs) genotypes revealed an association of PER2 SNP rs80136044, and SNP rs4128839, located 41.6 kb downstream of neuropeptide Y receptor type 1 gene, NPY1R (p = 3.4 × 10-6, OR = 11.4, 95% CI 2.7-48.2). The study provides preliminary insight into the relationship between genetic variants in circadian rhythm genes and long non-coding RNA (lncRNAs) in their vicinity, and opioid addiction.
Identifiants
pubmed: 31689297
doi: 10.1371/journal.pone.0224399
pii: PONE-D-19-23733
pmc: PMC6830932
doi:
Substances chimiques
3' Untranslated Regions
0
Basic Helix-Loop-Helix Transcription Factors
0
HES6 protein, human
0
PER2 protein, human
0
Period Circadian Proteins
0
RNA, Long Noncoding
0
Receptors, Vasoactive Intestinal Peptide, Type II
0
Repressor Proteins
0
VIPR2 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0224399Subventions
Organisme : NIDA NIH HHS
ID : UG1 DA015831
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA013046
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA015831
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA013732
Pays : United States
Organisme : NIDA NIH HHS
ID : UG1 DA013720
Pays : United States
Organisme : NIDA NIH HHS
ID : HHSN271201500065C
Pays : United States
Organisme : NIDA NIH HHS
ID : UG1 DA013034
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA013045
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA013034
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA015833
Pays : United States
Organisme : NIDA NIH HHS
ID : HHSN271201200017C
Pays : United States
Organisme : NIDA NIH HHS
ID : UG1 DA013732
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA013714
Pays : United States
Organisme : NIDA NIH HHS
ID : UG1 DA013714
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA013035
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024143
Pays : United States
Organisme : NIDA NIH HHS
ID : U10 DA013720
Pays : United States
Organisme : NIDA NIH HHS
ID : UG1 DA013035
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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