Methamphetamine and Other Substance Use Disorder Genetics in Thailand
泰国的甲基苯丙胺和其他药物使用障碍遗传学
基本信息
- 批准号:10585560
- 负责人:
- 金额:$ 86.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-06-15 至 2028-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAfrican ancestryAsiaAsianAsian ancestryAsian populationBehaviorBiologyChromosome MappingClinicalCollaborationsCollectionCommunitiesCopy Number PolymorphismCountryDNADataData SetDedicationsDiagnosisDiseaseDrug Use DisorderDrug abuseEast AsianEpidemicEuropean ancestryFacultyGeneticGenetic DiseasesGenetic RiskGenetic studyGenomicsGenotypeGrantHeritabilityHeterogeneityHospitalsHumanHuman GeneticsIndividualInfrastructureInternationalKnowledgeMapsMedicineMemoryMental HealthMental disordersMeta-AnalysisMethamphetamineMethamphetamine use disorderMethodsModelingNeurobiologyParticipantPatternPharmaceutical PreparationsPhenotypePopulationPreventionPrincipal InvestigatorPsychiatric HospitalsPsychopathologyPublic HealthResearchSamplingSampling StudiesSiteSubstance Use DisorderTaiwanThailandTimeUnderrepresented PopulationsUniversitiesVariantVeteransWorkbiobankcausal variantcohortcostdisorder controldisorder riskgene discoverygenetic analysisgenetic risk factorgenome analysisgenome sequencinggenome wide association studygenome-wideimprovedin silicoinstrumentneuroimagingphenomepleiotropismprogramspsychiatric genomicsrecruitrisk variantsample collectionsubstance usetraitwhole genome
项目摘要
Project Summary
Methamphetamine use disorder (MUD) is a hugely destructive public health problem that is surging worldwide,
including in many parts of the US and Asia. Thailand is an optimal site for studying the genetics of MUD, owing
to lower genetic and environmental heterogeneity than in the US, and lower research costs, in the greater
context of a devastating and widespread Thai epidemic of MUD, The Principal Investigators have formed the
international relationships and established the logistical infrastructures necessary for human genetic studies of
drug use disorders, including MUD, in Thailand, as shown during the prior iteration of this project; we collected
>4000 MUD-informative subjects (cases and exposed controls), twice the promised sample. Leveraging our
established and effective collaborations (Thanyarak Institute and Chulalongkorn University in Bangkok; Suan
Prung Hospital in Chiang Mai), our successful prior work supports the feasibility of this project. We will collect
and characterize a biobank sample for studies of substance use disorders (SUDs), especially MUD, as well as
other psychiatric disorders and behaviors. 6000 subjects will be recruited in Bangkok (primarily at SUD
treatment facilities) and 4000 in Chiang Mai (at Suan Prung, the major psychiatric hospital in the north of
Thailand and in the community); 10,000 in total, balanced with equal numbers of cases and non-MUD matched
controls. Subjects will be evaluated via the Thai MIND biobank instrument (the Thai version of an instrument
developed for a Million Veteran Program (MVP) project from previously-validated assessment modules). All
subjects' DNA will then be subjected to 3x low-pass whole-genome sequencing (WGS) at the Yale Center for
Genome Analysis, variants called, and the dataset subjected to genomewide association analyses. WGS will
allow the identification of common, rare, and copy number variants. We will undertake meta-analysis with other
East Asian (e.g. Taiwan – 2200 cases, 4400 controls) populations to increase power, and conduct trans-
ancestry meta-analyses with diverse ancestry groups (from the MVP sample and other large-scale biobanks
and cohorts). Following the identification of risk variants, we will use multiple approaches to investigate and
model MUD and other SUD polygenicity, and pleiotropy more broadly. We will also investigate the relationship
between genetic risk for MUD and other psychiatric traits, and implement causal inference analysis to
disentangle the pleiotropy of MUD with other psychiatric traits and disorders. Combining our newly-recruited
Thai cohort with our earlier Thai sample and other samples of diverse ancestral backgrounds will permit us to
fine-map MUD-associated loci and identify causal alleles across ancestry-specific LD patterns. Data will be
made available to the Psychiatric Genomics Consortium and results shared broadly. Results from this study
have the potential to advance greatly our understanding of genetic risk factors for MUD, especially in East
Asian populations underrepresented in genetic studies, leading to an improved understanding of the
neurobiology of MUD and, ultimately, improved approaches to its diagnosis, treatment, and prevention.
项目摘要
甲基苯丙胺使用障碍(MUD)是一个破坏性极大的公共卫生问题,正在全球范围内激增,
包括在美国和亚洲的许多地区。泰国是研究泥浆遗传学的最佳地点,因为
比美国更低的遗传和环境异质性,以及更低的研究成本
在泰国毁灭性和广泛流行的泥浆疫情的背景下,首席调查人员已经成立了
国际关系,并建立了人类基因研究所需的后勤基础设施
在泰国的药物使用障碍,包括泥浆,如在这个项目的前一次迭代中所示;我们收集了
>;4000名提供泥浆信息的受试者(病例和暴露的对照),是承诺样本的两倍。利用我们的
已建立和有效的合作(坦亚拉克研究所和曼谷的朱拉隆功大学;Suan
清迈的Prung医院),我们成功的前期工作支持了这个项目的可行性。我们会收集
以及用于物质使用障碍(SODS)研究的生物库样本的特征,特别是泥浆,以及
其他精神障碍和行为。将在曼谷招募6000名受试者(主要在南德
治疗设施)和4000人(在清迈北部的主要精神病院Suan Prung
泰国和社区);总共10,000例,病例数量相等,非泥浆匹配
控制。受试者将通过泰国思维生物库仪器(泰国版本的仪器)进行评估
根据先前验证的评估模块为百万退伍军人计划(MVP)项目开发)。全
受试者的DNA随后将在耶鲁大学中心接受3倍低通全基因组测序(WGS)
基因组分析,称为变异体,以及接受全基因组关联分析的数据集。WGS将
允许识别常见的、罕见的和拷贝数变体。我们将与其他公司进行荟萃分析
东亚(如台湾-2200例,4400例对照)人口增加权力,并进行跨国
不同祖先群体的祖先荟萃分析(来自MVP样本和其他大型生物库
和队列)。在确定风险变量之后,我们将使用多种方法来调查和
模拟泥浆和其他南泥的多源性,以及更广泛的多效性。我们还将调查两国关系
MUD的遗传风险与其他精神特征之间的关系,并进行因果推断分析
将MUD的多效性与其他精神特征和障碍分开。结合我们新招募的
与我们早先的泰国样本和其他具有不同祖先背景的样本的泰国队列将使我们能够
精细绘制MUD相关基因座图,并识别祖先特定LD模式的因果等位基因。数据将是
提供给精神病学基因组学联盟,并广泛分享结果。这项研究的结果
有可能极大地提高我们对MUD的遗传风险因素的理解,特别是在东部
亚洲人群在遗传学研究中的代表性不足,导致对
泥浆的神经生物学,并最终改进了其诊断、治疗和预防的方法。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population.
- DOI:10.1111/acer.13614
- 发表时间:2018-05
- 期刊:
- 影响因子:0
- 作者:Gelernter J;Zhou H;Nuñez YZ;Mutirangura A;Malison RT;Kalayasiri R
- 通讯作者:Kalayasiri R
Trends of cannabis use and related harms before and after legalization for recreational purpose in a developing country in Asia.
- DOI:10.1186/s12889-023-15883-6
- 发表时间:2023-05-19
- 期刊:
- 影响因子:4.5
- 作者:Kalayasiri, Rasmon;Boonthae, Suriyan
- 通讯作者:Boonthae, Suriyan
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{{ truncateString('JOEL GELERNTER', 18)}}的其他基金
The Robert T. Malison Yale-Chulalongkorn Stress, Alcohol Use and Psychopathology Training Program
罗伯特·T·马利森耶鲁-朱拉隆功压力、酒精使用和精神病理学培训计划
- 批准号:
10665205 - 财政年份:2023
- 资助金额:
$ 86.18万 - 项目类别:
Genetics of Alcohol Dependence in African Americans: Recruitment
非裔美国人酒精依赖的遗传学:招募
- 批准号:
10474310 - 财政年份:2018
- 资助金额:
$ 86.18万 - 项目类别:
Genetics of Alcohol Dependence in African Americans: Recruitment
非裔美国人酒精依赖的遗传学:招募
- 批准号:
9769607 - 财政年份:2018
- 资助金额:
$ 86.18万 - 项目类别:
Identifying Methamphetamine Risk Variants by Extreme Phenotype Exome Sequencing
通过极端表型外显子组测序识别甲基苯丙胺风险变异体
- 批准号:
9086352 - 财政年份:2015
- 资助金额:
$ 86.18万 - 项目类别:
Identifying Methamphetamine Risk Variants by Extreme Phenotype Exome Sequencing
通过极端表型外显子组测序识别甲基苯丙胺风险变异体
- 批准号:
9280890 - 财政年份:2015
- 资助金额:
$ 86.18万 - 项目类别:
Identifying Methamphetamine Risk Variants by Extreme Phenotype Exome Sequencing
通过极端表型外显子组测序识别甲基苯丙胺风险变异体
- 批准号:
9920116 - 财政年份:2015
- 资助金额:
$ 86.18万 - 项目类别:
Identifying Methamphetamine Risk Variants by Extreme Phenotype Exome Sequencing
通过极端表型外显子组测序识别甲基苯丙胺风险变异体
- 批准号:
9456704 - 财政年份:2015
- 资助金额:
$ 86.18万 - 项目类别:
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