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：
JOEL GELERNTER
金额：
$ 86.18万
依托单位：
YALE UNIVERSITY
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：
https://reporter.nih.gov/project-details/10585560
关键词：
Address African ancestry Asia Asian Asian ancestry Asian population Behavior Biology Chromosome Mapping Clinical Collaborations Collection Communities Copy Number Polymorphism Country DNA Data Data Set Dedications Diagnosis Disease Drug Use Disorder Drug abuse East Asian Epidemic European ancestry Faculty Genetic Genetic Diseases Genetic Risk Genetic study Genomics Genotype Grant Heritability Heterogeneity Hospitals Human Human Genetics Individual Infrastructure International Knowledge Maps Medicine Memory Mental Health Mental disorders Meta-Analysis Methamphetamine Methamphetamine use disorder Methods Modeling Neurobiology Participant Pattern Pharmaceutical Preparations Phenotype Population Prevention Principal Investigator Psychiatric Hospitals Psychopathology Public Health Research Sampling Sampling Studies Site Substance Use Disorder Taiwan Thailand Time Underrepresented Populations Universities Variant Veterans Work biobank causal variant cohort cost disorder control disorder risk gene discovery genetic analysis genetic risk factor genome analysis genome sequencing genome wide association study genome-wide improved in silico instrument neuroimaging phenome pleiotropism programs psychiatric genomics recruit risk variant sample collection substance use trait whole 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.

项目概要甲基苯丙胺使用障碍（MUD）是一个具有巨大破坏性的公共卫生问题，在全球范围内激增，包括美国和亚洲的许多地区，泰国是研究 MUD 遗传学的最佳地点。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 MUD 流行病肆虐且广泛蔓延的背景下，主要研究人员组成了国际关系并建立了人类遗传学研究所需的后勤基础设施泰国的药物使用障碍，包括 MUD，如我们在该项目的上一次迭代期间收集的数据所示； >4000 个 MUD 信息丰富的受试者（病例和暴露的对照），是我们承诺样本的两倍。建立和有效的合作（曼谷的 Thanyarak 学院和朱拉隆功大学；Suan 清迈 Prung 医院），我们之前的成功工作支持了该项目的可行性，我们将收集。并描述生物库样本的特征，用于研究物质使用障碍 (SUD)，特别是 MUD，以及其他精神疾病和行为将在曼谷招募 6000 名受试者（主要在 SUD）。治疗设施）以及清迈的 4000 名患者（位于泰国北部的主要精神病医院 Suan Prung）泰国和社区）；总共 10,000 个，病例数量相等且非 MUD 匹配受试者将通过泰国 MIND 生物库仪器（泰语版本的仪器）进行评估。为百万退伍军人计划 (MVP) 项目从先前验证的评估模块开发）。然后，受试者的 DNA 将在耶鲁中心进行 3 次低通全基因组测序 (WGS) 基因组分析，称为变体，并对数据集进行全基因组关联分析。允许识别常见、罕见和拷贝数变异。我们将与其他人一起进行荟萃分析。东亚（例如台湾 - 2200 例，4400 例对照）人口增加权力，并进行跨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）识别风险变异后，我们将使用多种方法进行调查和分析。模型 MUD 和其他 SUD 多基因性和多效性我们还将研究更广泛的关系。 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结合我们新招募的人员，解开 MUD 的多效性与其他精神特征和疾病。泰国队列与我们早期的泰国样本和其他不同祖先背景的样本将使我们能够精细绘制 MUD 相关位点并识别祖先特定 LD 模式的因果等位基因。该研究的结果已提供给精神病学基因组学联盟并得到广泛共享。有潜力极大地增进我们对 MUD 遗传风险因素的理解，特别是在东部地区亚洲人群在遗传学研究中的代表性不足，从而提高了对亚洲人群的了解 MUD 的神经生物学，并最终改进其诊断、治疗和预防方法。

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.

泰国人群酒精依赖及相关特征的全基因组关联研究。

DOI：
发表时间：
2018
期刊：
影响因子：
0
作者：
Gelernter, Joel;Zhou, Hang;Nuñez, Yaira Z;Mutirangura, Apiwat;Malison, Robert T;Kalayasiri, Rasmon
通讯作者：
Kalayasiri, Rasmon

Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.

汉族男性酒精依赖全基因组关联研究及跨民族多基因风险评分比较

DOI：
发表时间：
2019
期刊：
影响因子：
6.8
作者：
Sun, Yan;Chang, Suhua;Wang, Fan;Sun, Hongqiang;Ni, Zhaojun;Yue, Weihua;Zhou, Hang;Gelernter, Joel;Malison, Robert T;Kalayasiri, Rasmon;Wu, Ping;Lu, Lin;Shi, Jie
通讯作者：
Shi, Jie

Trends of cannabis use and related harms before and after legalization for recreational purpose in a developing country in Asia.

亚洲发展中国家娱乐目的大麻使用合法化前后的趋势及相关危害。