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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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 < 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0224399</identifier><identifier>PMID: 31689297</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2019-11, Vol.14 (11), p.e0224399</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Levran et al. 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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Levran et al 2019 Levran et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-27363a29f7385007019ada5ebbbd4bc8ef9262a1e0e031bcfd81701f4dc836f63</citedby><cites>FETCH-LOGICAL-c692t-27363a29f7385007019ada5ebbbd4bc8ef9262a1e0e031bcfd81701f4dc836f63</cites><orcidid>0000-0002-5136-4184</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830932/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830932/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31689297$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhang, Huiping</contributor><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><title>A 3' UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>3' Untranslated regions</subject><subject>3' Untranslated Regions - genetics</subject><subject>Addiction</subject><subject>Addictions</subject><subject>Adelson, Sheldon</subject><subject>Alcohol</subject><subject>Analysis</subject><subject>Autism</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Casein</subject><subject>Casein kinase I</subject><subject>Chromosomes</subject><subject>Circadian rhythm</subject><subject>Circadian Rhythm - genetics</subject><subject>Circadian rhythms</subject><subject>Cocaine</subject><subject>Coding</subject><subject>Drug abuse</subject><subject>Drug addiction</subject><subject>Gene expression</subject><subject>Gene mapping</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic polymorphisms</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic research</subject><subject>Genetic variance</subject><subject>Genomes</subject><subject>Genotypes</subject><subject>Genotyping</subject><subject>Heroin</subject><subject>Humans</subject><subject>Intestine</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Medicine and Health Sciences</subject><subject>Milk proteins</subject><subject>Narcotics</subject><subject>Neuropeptide Y</subject><subject>Neuropeptides</subject><subject>Non-coding RNA</subject><subject>Nucleotides</subject><subject>Opioid abuse</subject><subject>Opioid-Related Disorders - 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 - genetics</topic><topic>Addiction</topic><topic>Addictions</topic><topic>Adelson, Sheldon</topic><topic>Alcohol</topic><topic>Analysis</topic><topic>Autism</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Casein</topic><topic>Casein kinase I</topic><topic>Chromosomes</topic><topic>Circadian rhythm</topic><topic>Circadian Rhythm - genetics</topic><topic>Circadian rhythms</topic><topic>Cocaine</topic><topic>Coding</topic><topic>Drug abuse</topic><topic>Drug addiction</topic><topic>Gene expression</topic><topic>Gene mapping</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic polymorphisms</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic research</topic><topic>Genetic variance</topic><topic>Genomes</topic><topic>Genotypes</topic><topic>Genotyping</topic><topic>Heroin</topic><topic>Humans</topic><topic>Intestine</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Medicine and Health Sciences</topic><topic>Milk proteins</topic><topic>Narcotics</topic><topic>Neuropeptide Y</topic><topic>Neuropeptides</topic><topic>Non-coding RNA</topic><topic>Nucleotides</topic><topic>Opioid abuse</topic><topic>Opioid-Related Disorders - 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 & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & 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 & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & 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 & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & 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 < 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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identifier | ISSN: 1932-6203 |
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language | eng |
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source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
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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