Genome-Wide Association of Heroin Dependence in Han Chinese
Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to exam...
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| Published in | PloS one Vol. 11; no. 12; p. e0167388 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
09.12.2016
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1932-6203 1932-6203 |
| DOI | 10.1371/journal.pone.0167388 |
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| Abstract | Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field. |
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| AbstractList | Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes
CCDC42
(coiled coil domain 42;
p
= 2.8x10
-7
) and
BRSK2
(BR serine/threonine 2;
p
= 4.110
−6
). In addition, we found evidence for risk variants within the
ARHGEF10
(Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in
CCDC42
and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field. Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110−6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field. Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field. Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10 -7 ) and BRSK2 (BR serine/threonine 2; p = 4.110 −6 ). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field. Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10.sup.-7) and BRSK2 (BR serine/threonine 2; p = 4.110.sup.-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field. Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field.Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field. |
| Audience | Academic |
| Author | Wang, Yingcheng Kalsi, Gursharan Breen, Gerome Asherson, Philip Aliev, Fazil Ducci, Francesca Ma, Xiaohong Coleman, Jonathan R. I. Li, Tao Euesden, Jack Liu, Xiehe Collier, David A. Newhouse, Stephen J. |
| AuthorAffiliation | 2 MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom 4 Mental Health Center, West China Hospital, Sichuan University, Sichuan, People’s Republic of China 7 Department of Psychiatry, West China Hospital, School of Medicine, Sichuan University, Sichuan, People’s Republic of China 1 Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King’s College London, United Kingdom 3 Department of Actuarial Sciences and Risk Management, Faculty of Business, Karabuk University, Karabuk, Turkey 6 Lilly UK, Erl Wood Manor, Windlesham, Surrey, United Kingdom 5 Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, People’s Republic of China Johns Hopkins University Bloomberg School of Public Health, UNITED STATES |
| AuthorAffiliation_xml | – name: 1 Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King’s College London, United Kingdom – name: 2 MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom – name: 6 Lilly UK, Erl Wood Manor, Windlesham, Surrey, United Kingdom – name: Johns Hopkins University Bloomberg School of Public Health, UNITED STATES – name: 7 Department of Psychiatry, West China Hospital, School of Medicine, Sichuan University, Sichuan, People’s Republic of China – name: 3 Department of Actuarial Sciences and Risk Management, Faculty of Business, Karabuk University, Karabuk, Turkey – name: 5 Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, People’s Republic of China – name: 4 Mental Health Center, West China Hospital, Sichuan University, Sichuan, People’s Republic of China |
| Author_xml | – sequence: 1 givenname: Gursharan orcidid: 0000-0002-5156-7176 surname: Kalsi fullname: Kalsi, Gursharan – sequence: 2 givenname: Jack surname: Euesden fullname: Euesden, Jack – sequence: 3 givenname: Jonathan R. I. surname: Coleman fullname: Coleman, Jonathan R. I. – sequence: 4 givenname: Francesca surname: Ducci fullname: Ducci, Francesca – sequence: 5 givenname: Fazil surname: Aliev fullname: Aliev, Fazil – sequence: 6 givenname: Stephen J. surname: Newhouse fullname: Newhouse, Stephen J. – sequence: 7 givenname: Xiehe surname: Liu fullname: Liu, Xiehe – sequence: 8 givenname: Xiaohong surname: Ma fullname: Ma, Xiaohong – sequence: 9 givenname: Yingcheng surname: Wang fullname: Wang, Yingcheng – sequence: 10 givenname: David A. surname: Collier fullname: Collier, David A. – sequence: 11 givenname: Philip surname: Asherson fullname: Asherson, Philip – sequence: 12 givenname: Tao surname: Li fullname: Li, Tao – sequence: 13 givenname: Gerome surname: Breen fullname: Breen, Gerome |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27936112$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2016 Public Library of Science 2016 Kalsi 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. 2016 Kalsi et al 2016 Kalsi et al |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: We have the following interests. Prof David A. Collier is employed by Lilly UK and Dr Gerome Breen is a consultant with Lilly UK through his work on schizophrenia. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. These authors also contributed equally to this work. Conceptualization: GK GB.Data curation: GK GB.Formal analysis: GK JE JRIC FA SJN GB.Funding acquisition: GK DAC FD.Investigation: GK.Methodology: GK DAC GB.Project administration: GK PA.Resources: DAC XL XM YW TL.Software: JE JRIC GB.Supervision: PA GB.Validation: GK GB.Visualization: GK.Writing – original draft: GK.Writing – review & editing: GK GB. |
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| Snippet | Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new... |
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| SubjectTerms | Adult Asian People - genetics Association analysis Biology and Life Sciences Biomarkers China - epidemiology Chromosome 20 Chromosome 8 Diagnostic systems Dopamine Drug abuse Drug addiction Female Gene Frequency Genes Genetic aspects Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Genotypes Guanine Guanine nucleotide exchange factor Han (Chinese people) Health aspects Health care Heroin Heroin Dependence - epidemiology Heroin Dependence - genetics Humans Hypotheses Laboratories Linkage Disequilibrium Male Medicine and Health Sciences Mental disorders Mental health Narcotics Neurosciences People and places Polymorphism, Genetic Protein Serine-Threonine Kinases - genetics Psychiatry Rho Guanine Nucleotide Exchange Factors - genetics Risk analysis Risk factors Risk sharing Schizophrenia Serine Social Sciences Substance abuse Threonine Tobacco |
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| Title | Genome-Wide Association of Heroin Dependence in Han Chinese |
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