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Epigenome-wide association analyses of active injection drug use
Injection drug use (IDU) is prevalent in the US and is associated with substantial risk of blood-borne infections, morbidity, and mortality. However, the spectrum of its biologic effects on DNA methylation in blood is not well characterized. 401 participants (Mage = 47.9; 68% male; 90% African Ameri...
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Published in: | Drug and alcohol dependence 2022-06, Vol.235, p.109431-109431, Article 109431 |
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creator | Shu, Chang Jaffe, Andrew E. Sabunciyan, Sarven Ji, Hongkai Astemborski, Jacquie Sun, Jing Bakulski, Kelly M. Sosnowski, David W. Mehta, Shruti H. Kirk, Gregory D. Maher, Brion S. |
description | Injection drug use (IDU) is prevalent in the US and is associated with substantial risk of blood-borne infections, morbidity, and mortality. However, the spectrum of its biologic effects on DNA methylation in blood is not well characterized.
401 participants (Mage = 47.9; 68% male; 90% African American) over several timepoints (1054 visits) were drawn from a longitudinal cohort of people who inject drugs. DNA methylation was measured among buffy coat samples from the 1054 visits. Compared to samples collected after ≥ 6 months of abstinence, separate EWAS were conducted for active injecting of any drug, quantitative injection frequency, injecting of heroin and injecting of cocaine. Linear mixed effect models were used and analyses were adjusted for repeated measurements and key technical, biological, and sociodemographic characteristics.
We found epigenome-wide significant CpG sites associated with active injection (cg10636246, AIM2, p = 2.33 × 10−8) and injection intensity (cg13117953, p = 4.30 × 10−8). We found converging evidence that cg10636246 (AIM2), cg23110600 (PRKCH), cg03546163 (FKBP5), cg04590956 (GMCL1), and cg16317961 (MAPRE2) were among the top 0.1% significantly differentially methylated CpG sites shared across the five EWAS. Top ranked CpGs among the five EWAS were enriched (p |
doi_str_mv | 10.1016/j.drugalcdep.2022.109431 |
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401 participants (Mage = 47.9; 68% male; 90% African American) over several timepoints (1054 visits) were drawn from a longitudinal cohort of people who inject drugs. DNA methylation was measured among buffy coat samples from the 1054 visits. Compared to samples collected after ≥ 6 months of abstinence, separate EWAS were conducted for active injecting of any drug, quantitative injection frequency, injecting of heroin and injecting of cocaine. Linear mixed effect models were used and analyses were adjusted for repeated measurements and key technical, biological, and sociodemographic characteristics.
We found epigenome-wide significant CpG sites associated with active injection (cg10636246, AIM2, p = 2.33 × 10−8) and injection intensity (cg13117953, p = 4.30 × 10−8). We found converging evidence that cg10636246 (AIM2), cg23110600 (PRKCH), cg03546163 (FKBP5), cg04590956 (GMCL1), and cg16317961 (MAPRE2) were among the top 0.1% significantly differentially methylated CpG sites shared across the five EWAS. Top ranked CpGs among the five EWAS were enriched (p < 0.0001) in AIM2 inflammasome complex, T cell migration, insulin regulation and epinephrine synthesis pathways. During periods of active injection, samples had 0.46 years of epigenetic age acceleration relative to the abstinence period, within the same subject (p = 0.03).
Findings from this study demonstrate modest, common, and specific effects on DNA methylation during a relatively short time between periods of active drug injection and abstinence.
•Multiple DNA methylation sites are associated with active injection drug use•Top methylation sites are enriched in AIM2 inflammasome complex pathway•Within the same subjects, there was approximately a half year acceleration in biological age when comparing blood DNA methylation profiles during periods of active injection vs. abstinence</description><identifier>ISSN: 0376-8716</identifier><identifier>EISSN: 1879-0046</identifier><identifier>DOI: 10.1016/j.drugalcdep.2022.109431</identifier><identifier>PMID: 35395503</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Abstinence ; Adrenaline ; African Americans ; Biological effects ; Blood ; Buffy coat ; Cell migration ; Cocaine ; Cohort Studies ; CpG islands ; CpG Islands - genetics ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Drug abuse ; Drug use ; Epigenesis, Genetic ; Epigenetics ; Epigenome ; Epinephrine ; Female ; Genome-Wide Association Study ; Health risks ; Heroin ; Humans ; Inflammasomes ; Injection ; Injection drug use ; Insulin ; Lymphocytes ; Lymphocytes T ; Male ; Microtubule-Associated Proteins - genetics ; Middle Aged ; Morbidity ; Sociodemographics</subject><ispartof>Drug and alcohol dependence, 2022-06, Vol.235, p.109431-109431, Article 109431</ispartof><rights>2022 Elsevier B.V.</rights><rights>Copyright © 2022 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Jun 1, 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-a28ffea65f143c36b97f32e15399e070479c7e0867eab2f467c45c9320ff4e023</citedby><cites>FETCH-LOGICAL-c452t-a28ffea65f143c36b97f32e15399e070479c7e0867eab2f467c45c9320ff4e023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0376871622001685$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3547,27922,27923,30997,45778</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35395503$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shu, Chang</creatorcontrib><creatorcontrib>Jaffe, Andrew E.</creatorcontrib><creatorcontrib>Sabunciyan, Sarven</creatorcontrib><creatorcontrib>Ji, Hongkai</creatorcontrib><creatorcontrib>Astemborski, Jacquie</creatorcontrib><creatorcontrib>Sun, Jing</creatorcontrib><creatorcontrib>Bakulski, Kelly M.</creatorcontrib><creatorcontrib>Sosnowski, David W.</creatorcontrib><creatorcontrib>Mehta, Shruti H.</creatorcontrib><creatorcontrib>Kirk, Gregory D.</creatorcontrib><creatorcontrib>Maher, Brion S.</creatorcontrib><title>Epigenome-wide association analyses of active injection drug use</title><title>Drug and alcohol dependence</title><addtitle>Drug Alcohol Depend</addtitle><description>Injection drug use (IDU) is prevalent in the US and is associated with substantial risk of blood-borne infections, morbidity, and mortality. However, the spectrum of its biologic effects on DNA methylation in blood is not well characterized.
401 participants (Mage = 47.9; 68% male; 90% African American) over several timepoints (1054 visits) were drawn from a longitudinal cohort of people who inject drugs. DNA methylation was measured among buffy coat samples from the 1054 visits. Compared to samples collected after ≥ 6 months of abstinence, separate EWAS were conducted for active injecting of any drug, quantitative injection frequency, injecting of heroin and injecting of cocaine. Linear mixed effect models were used and analyses were adjusted for repeated measurements and key technical, biological, and sociodemographic characteristics.
We found epigenome-wide significant CpG sites associated with active injection (cg10636246, AIM2, p = 2.33 × 10−8) and injection intensity (cg13117953, p = 4.30 × 10−8). We found converging evidence that cg10636246 (AIM2), cg23110600 (PRKCH), cg03546163 (FKBP5), cg04590956 (GMCL1), and cg16317961 (MAPRE2) were among the top 0.1% significantly differentially methylated CpG sites shared across the five EWAS. Top ranked CpGs among the five EWAS were enriched (p < 0.0001) in AIM2 inflammasome complex, T cell migration, insulin regulation and epinephrine synthesis pathways. During periods of active injection, samples had 0.46 years of epigenetic age acceleration relative to the abstinence period, within the same subject (p = 0.03).
Findings from this study demonstrate modest, common, and specific effects on DNA methylation during a relatively short time between periods of active drug injection and abstinence.
•Multiple DNA methylation sites are associated with active injection drug use•Top methylation sites are enriched in AIM2 inflammasome complex pathway•Within the same subjects, there was approximately a half year acceleration in biological age when comparing blood DNA methylation profiles during periods of active injection vs. abstinence</description><subject>Abstinence</subject><subject>Adrenaline</subject><subject>African Americans</subject><subject>Biological effects</subject><subject>Blood</subject><subject>Buffy coat</subject><subject>Cell migration</subject><subject>Cocaine</subject><subject>Cohort Studies</subject><subject>CpG islands</subject><subject>CpG Islands - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Drug abuse</subject><subject>Drug use</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Epigenome</subject><subject>Epinephrine</subject><subject>Female</subject><subject>Genome-Wide Association Study</subject><subject>Health risks</subject><subject>Heroin</subject><subject>Humans</subject><subject>Inflammasomes</subject><subject>Injection</subject><subject>Injection drug use</subject><subject>Insulin</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Middle Aged</subject><subject>Morbidity</subject><subject>Sociodemographics</subject><issn>0376-8716</issn><issn>1879-0046</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>7QJ</sourceid><recordid>eNqFkMtKAzEUhoMoWi-vIANu3EzNbZLJTi31AoIbXYc0cyIZppOadCp9e1NbFdyYTSDn-885-RAqCB4TTMRVO27i8GY628BiTDGl-VlxRvbQiNRSlRhzsY9GmElR1pKII3ScUovzEQofoiNWMVVVmI3Q9XTh36APcyg_fAOFSSlYb5Y-9IXpTbdOkIrgCmOXfgWF71uwX8XNAsWQ4BQdONMlONvdJ-j1bvoyeSifnu8fJzdPpeUVXZaG1s6BEZUjnFkmZko6RoHkRRRgiblUVgKuhQQzo44LmXNWMYqd44ApO0GX276LGN4HSEs998lC15kewpA0FbyuVW6DM3rxB23DEPNnNpSsKJdCkUzVW8rGkFIEpxfRz01ca4L1xrJu9a9lvbGst5Zz9Hw3YJjNofkJfmvNwO0WgGxk5SHqZD30Fhofsz_dBP__lE94OZGW</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Shu, Chang</creator><creator>Jaffe, Andrew E.</creator><creator>Sabunciyan, Sarven</creator><creator>Ji, Hongkai</creator><creator>Astemborski, Jacquie</creator><creator>Sun, Jing</creator><creator>Bakulski, Kelly M.</creator><creator>Sosnowski, David W.</creator><creator>Mehta, Shruti H.</creator><creator>Kirk, Gregory D.</creator><creator>Maher, Brion S.</creator><general>Elsevier B.V</general><general>Elsevier Science Ltd</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>7QJ</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20220601</creationdate><title>Epigenome-wide association analyses of active injection drug use</title><author>Shu, Chang ; Jaffe, Andrew E. ; Sabunciyan, Sarven ; Ji, Hongkai ; Astemborski, Jacquie ; Sun, Jing ; Bakulski, Kelly M. ; Sosnowski, David W. ; Mehta, Shruti H. ; Kirk, Gregory D. ; Maher, Brion S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-a28ffea65f143c36b97f32e15399e070479c7e0867eab2f467c45c9320ff4e023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Abstinence</topic><topic>Adrenaline</topic><topic>African Americans</topic><topic>Biological effects</topic><topic>Blood</topic><topic>Buffy coat</topic><topic>Cell migration</topic><topic>Cocaine</topic><topic>Cohort Studies</topic><topic>CpG islands</topic><topic>CpG Islands - genetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Drug abuse</topic><topic>Drug use</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Epigenome</topic><topic>Epinephrine</topic><topic>Female</topic><topic>Genome-Wide Association Study</topic><topic>Health risks</topic><topic>Heroin</topic><topic>Humans</topic><topic>Inflammasomes</topic><topic>Injection</topic><topic>Injection drug use</topic><topic>Insulin</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Middle Aged</topic><topic>Morbidity</topic><topic>Sociodemographics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shu, Chang</creatorcontrib><creatorcontrib>Jaffe, Andrew E.</creatorcontrib><creatorcontrib>Sabunciyan, Sarven</creatorcontrib><creatorcontrib>Ji, Hongkai</creatorcontrib><creatorcontrib>Astemborski, Jacquie</creatorcontrib><creatorcontrib>Sun, Jing</creatorcontrib><creatorcontrib>Bakulski, Kelly M.</creatorcontrib><creatorcontrib>Sosnowski, David W.</creatorcontrib><creatorcontrib>Mehta, Shruti H.</creatorcontrib><creatorcontrib>Kirk, Gregory D.</creatorcontrib><creatorcontrib>Maher, Brion S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Applied Social Sciences Index & Abstracts (ASSIA)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Drug and alcohol dependence</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shu, Chang</au><au>Jaffe, Andrew E.</au><au>Sabunciyan, Sarven</au><au>Ji, Hongkai</au><au>Astemborski, Jacquie</au><au>Sun, Jing</au><au>Bakulski, Kelly M.</au><au>Sosnowski, David W.</au><au>Mehta, Shruti H.</au><au>Kirk, Gregory D.</au><au>Maher, Brion S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenome-wide association analyses of active injection drug use</atitle><jtitle>Drug and alcohol dependence</jtitle><addtitle>Drug Alcohol Depend</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>235</volume><spage>109431</spage><epage>109431</epage><pages>109431-109431</pages><artnum>109431</artnum><issn>0376-8716</issn><eissn>1879-0046</eissn><abstract>Injection drug use (IDU) is prevalent in the US and is associated with substantial risk of blood-borne infections, morbidity, and mortality. However, the spectrum of its biologic effects on DNA methylation in blood is not well characterized.
401 participants (Mage = 47.9; 68% male; 90% African American) over several timepoints (1054 visits) were drawn from a longitudinal cohort of people who inject drugs. DNA methylation was measured among buffy coat samples from the 1054 visits. Compared to samples collected after ≥ 6 months of abstinence, separate EWAS were conducted for active injecting of any drug, quantitative injection frequency, injecting of heroin and injecting of cocaine. Linear mixed effect models were used and analyses were adjusted for repeated measurements and key technical, biological, and sociodemographic characteristics.
We found epigenome-wide significant CpG sites associated with active injection (cg10636246, AIM2, p = 2.33 × 10−8) and injection intensity (cg13117953, p = 4.30 × 10−8). We found converging evidence that cg10636246 (AIM2), cg23110600 (PRKCH), cg03546163 (FKBP5), cg04590956 (GMCL1), and cg16317961 (MAPRE2) were among the top 0.1% significantly differentially methylated CpG sites shared across the five EWAS. Top ranked CpGs among the five EWAS were enriched (p < 0.0001) in AIM2 inflammasome complex, T cell migration, insulin regulation and epinephrine synthesis pathways. During periods of active injection, samples had 0.46 years of epigenetic age acceleration relative to the abstinence period, within the same subject (p = 0.03).
Findings from this study demonstrate modest, common, and specific effects on DNA methylation during a relatively short time between periods of active drug injection and abstinence.
•Multiple DNA methylation sites are associated with active injection drug use•Top methylation sites are enriched in AIM2 inflammasome complex pathway•Within the same subjects, there was approximately a half year acceleration in biological age when comparing blood DNA methylation profiles during periods of active injection vs. abstinence</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>35395503</pmid><doi>10.1016/j.drugalcdep.2022.109431</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Abstinence Adrenaline African Americans Biological effects Blood Buffy coat Cell migration Cocaine Cohort Studies CpG islands CpG Islands - genetics Deoxyribonucleic acid DNA DNA Methylation Drug abuse Drug use Epigenesis, Genetic Epigenetics Epigenome Epinephrine Female Genome-Wide Association Study Health risks Heroin Humans Inflammasomes Injection Injection drug use Insulin Lymphocytes Lymphocytes T Male Microtubule-Associated Proteins - genetics Middle Aged Morbidity Sociodemographics |
title | Epigenome-wide association analyses of active injection drug use |
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