Genome-Wide Association Study of HIV-1 Host Genetics Among Injection Drug Users
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ABSTRACT: The overarching goal of this project is to identify and characterize genetic determinants of HIV 1 susceptibility and resistance in samples of African American (AA) and European American (EA) injection drug users (IDUs) by conducting (1) a case/control genome-wide association (GWA) study of HIV 1 infection (positive/negative); (2) a case-only GWA study of viral load among HIV+ IDUs. The study uses existing samples and data from Urban Health Study (UHS) (PI: Alex Kral), which was the longest-running study of street-recruited IDUs in North America, from 1986-2005. UHS was a serial, cross-sectional sero-epidemiological study. Data were collected every 6 months in communities with a high prevalence of injection drug use in the San Francisco Bay Area. It used targeted sampling in neighborhoods at easily accessible community field sites, such as churches, single room occupancy hotels, and community centers. Eligibility criteria for initial entry to the study were (1) injection drug use in past 30 days; (2) ability to provide informed consent; and (3) age 18 or older. The UHS cohort includes over 9,000 African American and European American IDUs whose serum samples have been stored and data are available on HIV antibody status, HIV risk behaviors, drug abuse and demographics. The current study includes 984 HIV+ cases and 2,243 HIV- controls. Approximately two HIV- controls per case were frequency matched on: (1) self-reported ancestry; (2) sex; (3) age; (4) year of ascertainment; and (5) HIV risk class. This GWAS (DA026141) was funded by the National Institute on Drug Abuse (NIDA; PI: Eric O. Johnson). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR), was provided by NIDA and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C).
PROVIDER: phs000454.v1.p1 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:<p>The overarching goal of this project is to identify and characterize genetic determinants of HIV 1 susceptibility and resistance in samples of African American (AA) and European American (EA) injection drug users (IDUs) by conducting (1) a case/control genome-wide association (GWA) study of HIV 1 infection (positive/negative); (2) a case-only GWA study of viral load among HIV+ IDUs. The study uses existing samples and data from Urban Health Study (UHS) (PI: Alex Kral), which was the longest-running study of street-recruited IDUs in North America, from 1986-2005. UHS was a serial, cross-sectional sero-epidemiological study. Data were collected every 6 months in communities with a high prevalence of injection drug use in the San Francisco Bay Area. It used targeted sampling in neighborhoods at easily accessible community field sites, such as churches, single room occupancy hotels, and community centers. Eligibility criteria for initial entry to the study were (1) injection drug use in past 30 days; (2) ability to provide informed consent; and (3) age 18 or older. The UHS cohort includes over 9,000 African American and European American IDUs whose serum samples have been stored and data are available on HIV antibody status, HIV risk behaviors, drug abuse and demographics.</p> <p>The current study includes 984 HIV+ cases and 2,243 HIV- controls. Approximately two HIV- controls per case were frequency matched on: (1) self-reported ancestry; (2) sex; (3) age; (4) year of ascertainment; and (5) HIV risk class. This GWAS (DA026141) was funded by the National Institute on Drug Abuse (NIDA; PI: Eric O. Johnson). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR), was provided by NIDA and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C). </p>
| phs000454 | dbGaP
Project description:<p>The <b>A</b>IDS <b>L</b>inked to the <b>I</b>ntravenous <b>E</b>xperience (<b>ALIVE</b>) Study is a long-standing community based research effort that includes past and current injection drug users (IDUs). ALIVE has been ongoing since 1988 and is one of the longest-running community-based cohorts of IDUs in existence. The primary objectives when the study started were to characterize the incidence and natural history of HIV among injection drug users (IDUs). At each study visit, participants undergo a series of questionnaires that elicit information about substance use (including drugs used and route of administration) and a blood draw. A subsample of 1200 subjects was selected for genotyping for the NIDA Smokescreen effort who report heroin injection and have existing peripheral blood samples (isolated buffy coat). In addition to injected heroin, ALIVE subjects are assessed on lifetime and previous six months use of marijuana (76.3%), crack (55.5%), snorted cocaine (48.3%), injected cocaine (89.9%), injected speedball (87.0%), and smoking heroin (9.0%). The sample is 33.4% female, ~85% African-American and assessed through a mean maximum age of 49.9 years old. Importantly, subjects are not assessed to meet DSM criteria, but all subjects report having injected drugs. We provide demographic data (age at assessment, sex, self-reported race) and drug use data (lifetime "use" ever endorsed) for each drug class/route described above for each subject</p>
| phs001494 | dbGaP
Project description:CIDR-NIDA Study of HIV Host Genetics
| PRJNA83629 | ENA
Project description:Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modelling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative RT-PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of patients. A similar functional activation of the “immunological disease” category was evident when we compared patients according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the patients. Mn-methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections. However, despite the strong confounding effect from infection, some modest drug abuse effects on gene expression were detected. 40 samples, 20 healthy volunteers and 20 illicit methcathinone users
2011-04-19 | E-GEOD-28686 | biostudies-arrayexpress
Project description:HIV transmission involves the adhesion to and migration of infected cells, including monocytes across biological barriers comprising extracellular matrix components. Recently, semen exosomes (SE) from HIV uninfected (HIV-) and HIV infected (HIV+) subjects were shown to contain molecules that were adhesive to Jurkat T cells. Since monocyte trafficking across various biological barriers are intensified by HIV and/or illicit substances, such as cocaine, we sought to understand how SE from HIV infected subjects’ comorbid with illicit drug abuse influence monocyte gene expression and behavior. Therefore, a model of U937 monocyte adhesion on collagen-coated surface in the presence and absence of SE from various clinical (HIV-Drug-, HIV-Drug+, HIV+Drug-, and HIV+Drug+) groups was developed. Using this system, we demonstrate by Microarray analysis that SE from different clinical groups reprogramed gene expression profile of monocytes cultured atop collagen. In line with altered gene expression is increased adhesion of monocytes to collagen following treatment with SE from all clinical groups compared to vehicle. Interestingly, SE from HIV+ subjects’ comorbid with drug abuse potentiated monocyte adhesion to collagen. Mechanistically, SE-Drug and SE-HIV altered monocyte shape, induced actin cytoskeleton reorganization, formation of membrane ruffles and lamellipodia-like structures, as well as focal-adhesion contacts. The cytoskeletal reorganization induced by SE-Drug is associated with impairment of cell motility, while SE-HIV increased cell chemotaxis toward HIV secretome. The observation of SE-Drug and SE-HIV mediated alteration of monocyte transcriptome and cellular behavior reported herein is key to understanding the contribution of exosomes to long-term neuro, vascular, and mucosal perturbations associated with psychostimulants (methamphetamine, cocaine, opioids, and alcohol) comorbidity with HIV infection.
2019-09-20 | GSE129506 | GEO
Project description:Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modelling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative RT-PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of patients. A similar functional activation of the “immunological disease” category was evident when we compared patients according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the patients. Mn-methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections. However, despite the strong confounding effect from infection, some modest drug abuse effects on gene expression were detected.
2011-04-19 | GSE28686 | GEO
Project description:Disruption of the cerebrovascular integrity is involved in the context of drug abuse. Our study provides a potential new therapeutic strategy to cerebrovascular damage in the context of drug abuse.
2020-03-10 | GSE96063 | GEO
Project description:<p>This study is part of the Gene Environment Association Studies initiative (GENEVA) funded by the National Human Genome Research Institute. The overarching goal is to identify novel genetic factors that contribute to addiction through a large-scale genome-wide association study of DSM-IV alcohol dependent (and frequently illicit drug dependent) cases and non-dependent, unrelated control subjects of European and African American descent.</p> <p>The focus of this proposal is a case-control design of unrelated individuals for a genetic association study of addiction. Cases are defined as individuals with DSM-IV alcohol dependence (lifetime) and potentially other illicit drug dependence. In addition to the categorical diagnosis, we have data on ordinal measurements of number of DSM-IV symptoms for alcohol, nicotine, marijuana, cocaine, opiates and other drugs so that we will able to construct quantitative measurements of addiction severity over a wide range of substances. Controls are defined as individuals who have been exposed to alcohol (and possibly to other drugs), but have never met lifetime diagnosis for alcohol dependence or dependence on other illicit substances. Analyses that include refinement of the phenotype and incorporation of important demographic and environmental factors into association studies will be pursued.</p> <p>Cases and controls were selected from three large, complementary datasets: the Collaborative Study on the Genetics of Alcoholism (COGA), the Family Study of Cocaine Dependence (FSCD), and the Collaborative Genetic Study of Nicotine Dependence (COGEND).</p> <p><b><u>COGA:</u></b> COGA was initiated in 1989 and is a large-scale family study that has had as its primary aim the identification of genes that contribute to alcoholism susceptibility and related characteristics. COGA is funded through the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Subjects were recruited from 7 sites across the U.S. Alcohol dependent probands were recruited from treatment facilities and assessed by personal interview. After securing permission, other family members were also assessed. A set of comparison families was drawn from the same communities as the families recruited through the alcohol dependent probands. Assessment involved a comprehensive personal interview developed for this project, the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), which gathers detailed information on alcoholism related symptoms along with other drugs and psychiatric symptoms. Families with three or more first-degree relatives who were alcohol dependent were invited for more extensive testing, including neurophysiology evaluations (ERPs and EEGs) and a battery of neuropsychological assessments. Blood was obtained for genetic studies. Institutional Review Boards at all sites approved the protocols, including sharing in the NIAAA national repository.</p> <p>COGA has four Co-Principal Investigators Bernice Porjesz, Victor Hesselbrock, Howard Edenberg, and Laura Bierut. COGA includes nine different centers where data collection, analysis, and storage take place. The nine sites and Principal Investigators and Co-investigators are: University of Connecticut (Victor Hesselbrock); Indiana University (Howard Edenberg, John Nurnberger, Jr., Tatiana Foroud); University of Iowa (Samuel Kuperman); SUNY Downstate (Bernice Porjesz); Washington University in St. Louis (Laura Bierut, Alison Goate, John Rice); University of California at San Diego (Marc Schuckit); Howard University (Robert Taylor); Rutgers University (Jay Tischfield); Southwest Foundation (Laura Almasy). Q. Max Guo serves as the NIAAA Staff Collaborator. This national collaborative study is supported by the NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA).</p> <p><b><u>Family Study of Cocaine Dependence (FSCD):</u></b> This project was initiated in 2000 as a case-control family study of cocaine dependence funded through the National Institute on Drug Abuse (NIDA; PI: Laura Bierut). The primary goal was to increase the understanding of the familial and non-familial antecedents and consequences of cocaine dependence. Cocaine dependent individuals were systematically recruited from chemical dependency treatment units (both public and private; residential and outpatient) in the greater St. Louis metropolitan area. Community based control subjects were identified through a Missouri Driver's License Registry (maintained at Washington University for research purposes) and matched by age, race, gender, and residential zip code. As a supplement to this project, blood samples were collected for future genetic analysis and were included in the NIDA Genetics Consortium. Phenotypic data, DNA, and cell lines are in the NIDA Center for Genetics Studies.</p> <p><b><u>Collaborative Genetic Study of Nicotine Dependence (COGEND):</u></b> COGEND was initiated in 2001 as a three-part program project grant funded through the National Cancer Institute (NCI; PI: Laura Bierut). The three projects included a study of the familial transmission of nicotine dependence, a genetic study of nicotine dependence, and a study of the relationship of nicotine dependence with nicotine metabolism. The primary goal is to detect, localize, and characterize genes that predispose or protect an individual with respect to heavy tobacco consumption, nicotine dependence, and related phenotypes and to integrate these findings with the family transmission and nicotine metabolism findings. The primary design is a community based case-control family study. All subjects were recruited from Detroit and St. Louis. Nicotine dependent cases and non-dependent smoking controls were identified and recruited. In addition, one sibling for each case and control subject was recruited in a subset of the sample. Over 56,000 subjects aged 25-44 years were screened by telephone, over 3,100 subjects were personally interviewed, and over 2,900 donated blood samples for genetic studies.</p> <p>All three studies (COGA, COGEND, FSCD) include measures of basic socio-demographic variables, including age, sex, race/ethnicity, family income, educational attainment, religious participation, and family structure. Other important covariates and/or potential moderators of genetic effects include comorbid addictions and age at initiation of use for cigarettes, alcohol and drugs. The assessments also include measures of various life stressors, such as physical and sexual abuse, which have been implicated in gene-environment interactions for several disorders. Coding for both individual variables and indices has been standardized across studies. All subjects were assessed in person by trained research assistants.</p> <p>Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR), was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C).</p> <p><b>Note for Publications Related to Study:</b> The Study of Addiction: Genetics and Environment (SAGE) has not yet generated publications. Below is a listing of publications related to the three studies from which the SAGE sample was selected. COGA has over 228 publications listed at <a href="http://www.niaaagenetics.org" target="_blank">www.niaaagenetics.org</a></p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to addiction through a large-scale genome-wide association study of DSM-IV alcohol dependent (and frequently illicit drug dependent) cases and non-dependent, unrelated control subjects of European and African American descent. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>
| phs000092 | dbGaP
Project description:Both drugs abuse and HIV infection continue to affect many indiviiduals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse such as the psychostimulant methamphetamine. In order to determine the interaction of HIV and methamphetamine we isolated microglia and macrophages from the brains of SIV-infected rhesus monkeys treated with methamphetamine and from SIV-infected monkeys who did not receive methamphetamine. Cells were subjected to single cell RNA sequencing and results analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of cells were infected by SIV. In addition, genes encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of cells from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.
2020-12-01 | GSE160384 | GEO