A 3' UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction

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 addict...

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Veröffentlicht in:PloS one 2019-11, Vol.14 (11), p.e0224399
Hauptverfasser: Levran, Orna, Randesi, Matthew, Rotrosen, John, Ott, Jurg, Adelson, Miriam, Kreek, Mary Jeanne
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Randesi, Matthew
Rotrosen, John
Ott, Jurg
Adelson, Miriam
Kreek, Mary Jeanne
description 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.
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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 &lt; 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). 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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 &lt; 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). 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genetics</subject><subject>Opioids</subject><subject>Peptides</subject><subject>Period 2 protein</subject><subject>Period Circadian Proteins - genetics</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins</subject><subject>Quantitative trait loci</subject><subject>Quantitative Trait Loci - genetics</subject><subject>Receptors, Vasoactive Intestinal Peptide, Type II - genetics</subject><subject>Reinforcement</subject><subject>Repressor Proteins - genetics</subject><subject>Reward</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Long Noncoding - genetics</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Social Sciences</subject><subject>Stress response</subject><subject>Studies</subject><subject>Substance abuse treatment</subject><subject>Suprachiasmatic nucleus</subject><subject>Transcription</subject><subject>Vasoactive agents</subject><subject>Vasoactive intestinal peptide</subject><subject>Vasoactive intestinal peptides</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNku9rEzEYxw9R3Jz-B6KBgSKsNT-uudwboYyphbLNrtvb8Fx-tCnXS02uOv97U3sbPVCQvEh48nm-efjmm2WvCR4SVpCPK78NDdTDjW_MEFOas7J8kh2TktEBp5g9PTgfZS9iXGE8YoLz59kRI1yUtCyOszhG7D26nc_QzeU1ClGIkeDsDAFSLg7Mt_kUWR9QuzSpEBRoBw1amMagu8n1jCJoNKpdo2aXY5Q0z5CLCGL0ykFrNPrp2iXyG-edRqC1U63zzcvsmYU6mlfdfpLdfr6Yn38dTK--TM7H04HiJW0HtGCcAS1twcQI4wKTEjSMTFVVOq-UMLaknAIx2GBGKmW1IAmyuVaCccvZSfZ2r7upfZSdX1FSRpJbgrIyEZM9oT2s5Ca4NYRf0oOTfwo-LCSE1qnayJzqwgqmKwCda1GUHBONq8oWkNwsTNL61L22rdZGK9O0AeqeaP-mcUu58D8kFwynj0oCp51A8N-3Jrb_GLmjFpCmco31SUytXVRyzHEuRjlnRaKGf6HS0mbtVEqMdanea_jQa0hMa-7bBWxjlJOb2f-zV3d99t0BuzRQt8vo6-0uB7EP5ntQBR9jMPbROYLlLvAPbshd4GUX-NT25tD1x6aHhLPfh933Dw</recordid><startdate>20191105</startdate><enddate>20191105</enddate><creator>Levran, Orna</creator><creator>Randesi, Matthew</creator><creator>Rotrosen, John</creator><creator>Ott, Jurg</creator><creator>Adelson, Miriam</creator><creator>Kreek, Mary Jeanne</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5136-4184</orcidid></search><sort><creationdate>20191105</creationdate><title>A 3' UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction</title><author>Levran, Orna ; Randesi, Matthew ; Rotrosen, John ; Ott, Jurg ; Adelson, Miriam ; Kreek, Mary Jeanne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-27363a29f7385007019ada5ebbbd4bc8ef9262a1e0e031bcfd81701f4dc836f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>3' Untranslated regions</topic><topic>3' Untranslated Regions - 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genetics</topic><topic>Opioids</topic><topic>Peptides</topic><topic>Period 2 protein</topic><topic>Period Circadian Proteins - genetics</topic><topic>Physiological aspects</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proteins</topic><topic>Quantitative trait loci</topic><topic>Quantitative Trait Loci - genetics</topic><topic>Receptors, Vasoactive Intestinal Peptide, Type II - genetics</topic><topic>Reinforcement</topic><topic>Repressor Proteins - genetics</topic><topic>Reward</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Long Noncoding - genetics</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Social Sciences</topic><topic>Stress response</topic><topic>Studies</topic><topic>Substance abuse treatment</topic><topic>Suprachiasmatic nucleus</topic><topic>Transcription</topic><topic>Vasoactive agents</topic><topic>Vasoactive intestinal peptide</topic><topic>Vasoactive intestinal peptides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Levran, Orna</creatorcontrib><creatorcontrib>Randesi, Matthew</creatorcontrib><creatorcontrib>Rotrosen, John</creatorcontrib><creatorcontrib>Ott, Jurg</creatorcontrib><creatorcontrib>Adelson, Miriam</creatorcontrib><creatorcontrib>Kreek, Mary Jeanne</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - 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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 &lt; 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31689297</pmid><doi>10.1371/journal.pone.0224399</doi><tpages>e0224399</tpages><orcidid>https://orcid.org/0000-0002-5136-4184</orcidid><oa>free_for_read</oa></addata></record>
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subjects 3' Untranslated regions
3' Untranslated Regions - genetics
Addiction
Addictions
Adelson, Sheldon
Alcohol
Analysis
Autism
Basic Helix-Loop-Helix Transcription Factors - genetics
Biology
Biology and Life Sciences
Casein
Casein kinase I
Chromosomes
Circadian rhythm
Circadian Rhythm - genetics
Circadian rhythms
Cocaine
Coding
Drug abuse
Drug addiction
Gene expression
Gene mapping
Genes
Genetic aspects
Genetic diversity
Genetic polymorphisms
Genetic Predisposition to Disease
Genetic research
Genetic variance
Genomes
Genotypes
Genotyping
Heroin
Humans
Intestine
Kinases
Laboratories
Medicine and Health Sciences
Milk proteins
Narcotics
Neuropeptide Y
Neuropeptides
Non-coding RNA
Nucleotides
Opioid abuse
Opioid-Related Disorders - genetics
Opioids
Peptides
Period 2 protein
Period Circadian Proteins - genetics
Physiological aspects
Polymorphism, Single Nucleotide
Proteins
Quantitative trait loci
Quantitative Trait Loci - genetics
Receptors, Vasoactive Intestinal Peptide, Type II - genetics
Reinforcement
Repressor Proteins - genetics
Reward
Ribonucleic acid
RNA
RNA, Long Noncoding - genetics
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Social Sciences
Stress response
Studies
Substance abuse treatment
Suprachiasmatic nucleus
Transcription
Vasoactive agents
Vasoactive intestinal peptide
Vasoactive intestinal peptides
title A 3' UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
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