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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| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0199951 |
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Carl</contributor><creatorcontrib>Levran, Orna ; Correa da Rosa, Joel ; Randesi, Matthew ; Rotrosen, John ; Adelson, Miriam ; Kreek, Mary Jeanne ; Lin, Z. Carl</creatorcontrib><description>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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0199951</identifier><identifier>PMID: 29953524</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2018-06, Vol.13 (6), p.e0199951</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 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>2018 Levran et al 2018 Levran et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-7d4d56816c1fe6f7156d48e5f666fd928482fbe23c18d2ae2aac070eebb868d23</citedby><cites>FETCH-LOGICAL-c692t-7d4d56816c1fe6f7156d48e5f666fd928482fbe23c18d2ae2aac070eebb868d23</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/PMC6023117/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023117/$$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/29953524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lin, Z. Carl</contributor><creatorcontrib>Levran, Orna</creatorcontrib><creatorcontrib>Correa da Rosa, Joel</creatorcontrib><creatorcontrib>Randesi, Matthew</creatorcontrib><creatorcontrib>Rotrosen, John</creatorcontrib><creatorcontrib>Adelson, Miriam</creatorcontrib><creatorcontrib>Kreek, Mary Jeanne</creatorcontrib><title>A non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6, is associated with heroin addiction</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Addictions</subject><subject>Adelson, Sheldon</subject><subject>Alcohol</subject><subject>Alcoholic beverages</subject><subject>Anxiety</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Biology and life sciences</subject><subject>Care and treatment</subject><subject>Development and progression</subject><subject>Drug abuse</subject><subject>Drug addiction</subject><subject>Filtration</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Heroin</subject><subject>Heroin habit</subject><subject>Laboratories</subject><subject>Medicine and Health Sciences</subject><subject>Methadone</subject><subject>Minority & ethnic groups</subject><subject>Narcotics</subject><subject>Non-coding RNA</subject><subject>Permutations</subject><subject>Physical Sciences</subject><subject>Pituitary</subject><subject>Post traumatic stress disorder</subject><subject>Posttraumatic stress disorder</subject><subject>Principal components analysis</subject><subject>Psychiatry</subject><subject>Quantitative trait loci</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Social Sciences</subject><subject>Stress response</subject><subject>Stresses</subject><subject>Studies</subject><subject>Substance abuse 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non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6, is associated with heroin addiction</title><author>Levran, Orna ; Correa da Rosa, Joel ; Randesi, Matthew ; Rotrosen, John ; Adelson, Miriam ; Kreek, Mary Jeanne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-7d4d56816c1fe6f7156d48e5f666fd928482fbe23c18d2ae2aac070eebb868d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Addictions</topic><topic>Adelson, Sheldon</topic><topic>Alcohol</topic><topic>Alcoholic beverages</topic><topic>Anxiety</topic><topic>Bioinformatics</topic><topic>Biology</topic><topic>Biology and life sciences</topic><topic>Care and treatment</topic><topic>Development and progression</topic><topic>Drug abuse</topic><topic>Drug addiction</topic><topic>Filtration</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic 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Jeanne</au><au>Lin, Z. Carl</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6, is associated with heroin addiction</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-06-28</date><risdate>2018</risdate><volume>13</volume><issue>6</issue><spage>e0199951</spage><pages>e0199951-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29953524</pmid><doi>10.1371/journal.pone.0199951</doi><tpages>e0199951</tpages><orcidid>https://orcid.org/0000-0002-5136-4184</orcidid><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | A non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6, is associated with heroin addiction |
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