NIAAA Repository/Screening Database Management and Research

NIAAA 存储库/筛选数据库管理和研究

• 批准号: 9559245
• 负责人: Melanie Schwandt
• 金额: $ 723.84万
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9559245
• 关键词: Adult; Aggressive behavior; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Annual Reports; Anxiety; Archives; Attentional deficit; Behavior; Biochemical; Brain; C-reactive protein; Calcium; Caring; Characteristics; Clinic; Clinical; Clinical Research; Collaborations; Comorbidity; Consumption; Cyclic GMP; Data; Data Analyses; Data Base Management; Databases; Decision Making; Deposition; Desire for food; Development; Diagnosis; Disease; Dopamine; EF-Hand Domain; Eligibility Determination; Enrollment; Ensure; Environment; Epigenetic Process; Esthesia; Etiology; Evaluation; Exhibits; Factor Analysis; Family member; Fatty Acids; Feeling suicidal; Foundations; GABA Transporter 1; GABBR2 gene; GATA4 gene; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genomics; Genotype; Glucose; Goals; Heavy Drinking; Hepatic; Hereditary Disease; Heterogeneity; Hormones; Human; Human Genome; Hyperactive behavior; Impulsive Behavior; Impulsivity; Individual; Inpatients; Institutes; Journals; Laboratories; Laboratory Research; Leptin; Life Stress; Lipids; Manuscripts; Measures; Mediating; Mental Depression; Monitor; Montgomery and Asberg depression rating scale; National Institute of Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Natural History; Neurobiology; Obesity; Outcome; Pain; Participant; Pathway Analysis; Pathway interactions; Patients; Peer Review; Peptide Receptor; Personality; Phenotype; Post-Traumatic Stress Disorders; Preparation; Proprotein Convertases; Protein Analysis; Protein Kinase; Protocols documentation; Psychiatric Diagnosis; Public Health; Publications; Publishing; Quality of life; Recording of previous events; Reporting; Research; Research Personnel; Research Project Grants; Resource Sharing; Resources; Rewards; Risk Factors; Role; Safety; Series; Severities; Sex Characteristics; Sgk protein; Signal Transduction; Single Nucleotide Polymorphism; Sleep; Smoking; Social support; Standardization; Stimulus; Stress; Subgroup; Subtilisins; Suicide; Symptoms; Therapeutic; Trauma; United States; United States National Institutes of Health; Variant; Vasopressin Receptor; Vasopressins; Withdrawal; Work; acamprosate; addiction; alcohol behavior; alcohol response; alcohol screening; alcohol seeking behavior; alcohol use disorder; alpha synuclein gene; anxiety symptoms; behavioral health; biological adaptation to stress; clinical care; clinical phenotype; corticotropin releasing factor-binding protein; craving; data sharing; depressive symptoms; discount; discounting; dopamine transporter; drinking; epidemiology study; exome sequencing; experience; externalizing behavior; falls; fatty acid amide hydrolase; genetic analysis; genome wide association study; genomic data; ghrelin; high risk drinking; human data; hypocretin; insulin signaling; islet amyloid polypeptide; liver injury; netrin receptor; neurogenetics; neuroimaging; phenotypic data; prevent; problem drinker; programs; psychogenetics; quality assurance; receptor; repository; response; screening; sex; trait; vesicular monoamine transporter 1; volunteer

As of this report, the NIAAA Repository/Screening Database includes phenotype and/or genomic data on more than 2300 individuals. Phenotype data include psychiatric diagnoses, a number of alcohol-related assessments and measures including lifetime and recent consumption and alcohol response phenotypes, personality and impulsivity measures, depression and anxiety symptoms, current and early life stress and trauma, aggression, suicidality, smoking, IQ, sleep quality, pain, and overall quality of life. Laboratory/biochemical measures are also available. Genomic data include large-scale single nucleotide polymorphism (SNP) genotyping performed using Illumina arrays via a partnership between the Clinical Core Laboratory of the OCD, and the Laboratory of Neurogenetics (NIAAA). All NIAAA PI's are encouraged to submit data requests in order to conduct research projects and analyses using the shared NIAAA Repository/Screening Database. Projects are logged and the status is tracked from initial request to manuscript publication. In addition, Human and Genomic data are shared via BTRIS and other mechanisms, including collaboration with NIH-supported consortia (PGC Alcoholism, ENIGMA) to ensure data sharing. Development of standardized assessments of alcohol responses (Mini alcohol screening exam -MASE), neurobiological changes during the addiction cycle (Addictions Neuroclinical assessment -ANA) and measures of addiction are proceeding via the natural history protocol and also via neuroimaging studies in the OCD Neuroimaging core (PI, Reza Momenan). Using the clinical database, factor and pathway analyses are being performed to identify factors, and clinical subgroups within patients with AUD who are heterogeneous both etiologically and in terms of clinical outcome. I. Projects resulting in manuscripts published within the past year The development of the Addictions Neuroclinical assessment has resulted in two publications. A comparison of characteristics and clinical outcomes in alcoholic inpatients with and without comorbid posttraumatic stress disorder (PTSD) Effects of fatty acid amide hydrolase (FAAH) genetic variation and alcohol-related outcomes and severity of alcohol dependence Investigating the role of the Leu72Met polymorphism of the prepro-ghrelin gene in alcohol dependence and alcohol-related behaviors Effects of sex, drinking history, and fatty acids on liver injury in heavy drinking alcohol-dependent inpatients FAAH genetic variation, anxiety, and brain response to negative stimuli alcohol dependent inpatients with comorbid PTSD Effect of genetic variation in the vesicular monoamine transporter 1 (VMAT1/SLC18A1) gene on alcohol withdrawal severity Corticotropin releasing factor binding protein (CRF-BP) genetic variation in alcoholism and alcohol-related phenotypes A comparison of characteristics and clinical outcomes in treatment-seeking versus non treatment-seeking alcohol dependent individuals Hepatic, lipid and genetic factors associated with obesity and their association with alcohol dependence Assessment of the validity of the Montgomery-Asberg Depression Rating Scale (MADRS) in identifying depression diagnoses in alcohol dependent inpatients II. Projects resulting in manuscript submissions, or publications in press, within the past year There were three manuscripts submitted and/or accepted for publication in peer-reviewed journals during the reporting year that were the result of research projects using the NIAAA Repository/Screening Database. These projects include: The role of genetic variation and dysregulation of proprotein convertase subtilisin/kexin 9 (PCSK9) in alcoholism and alcohol-related phenotypes Impulsivity mediates the relationship of adult attention deficit hyperactivity symptoms and alcohol dependence severity Investigating the role of the cluster of differentiation 38 (CD38) rs3796863 polymorphism in alcohol and monetary reward: possible involvement of dopamine signaling III. Projects with manuscripts in preparation There are six projects with manuscripts in preparation: Early life stress is associated with suicidality in alcoholic inpatients Effects of the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile on severity of alcohol dependence and stress response in alcohol-dependent subjects. Association analysis of genetic variation in GATA Binding Protein 4 (GATA4) and alcohol use disorder Genetics and epigenetics of the dopamine transporter (DAT) in alcohol use disorder Obsessive craving as a predictor of suicidal ideation in alcohol dependent inpatients Assessment of Addictions Neuroclinical Assessment (ANA) domains using measures from the current NIAAA screening protocol IV. Ongoing projects still in progress There are four projects still ongoing from the previous year: GABA (GABBR1 and GABBR2) and GABA transporter 1 (GAT1) genetic variation in alcoholism and alcohol-related phenotypes. Data analyses are ongoing. Association between DCC netrin 1 receptor (DCC) and synuclein alpha (SNCA) genes and measures of impulsive behavior in alcoholic patients and controls. Data analyses are ongoing. Genetic variation in serum/glucocorticoid regulated kinase 1 (SGK1) and associated clinical phenotypes in alcohol use disorder. Data analyses are ongoing. Exome sequencing of alcoholic inpatients with low and high withdrawal. Sequencing is ongoing. V. New projects initiated within the past year There were eleven new research projects initiated during the reporting year: Genetics of vasopressin and vasopressin receptors in alcoholism. Data analyses are ongoing. The role of C-Reactive protein in alcohol use disorder. Data analyses are ongoing. Free peptide and receptor genotype of the appetitive hormones, leptin and amylin, and their association with alcohol-related phenotypes. Data analyses are ongoing. Calcium as a modulator of alcohol use disorder and the response to Acamprosate. Data analyses are ongoing. GWAS and pathway-informed analysis of externalizing behaviors. Data analyses are ongoing. Sex differences in glucose and insulin signaling and their association with trait aggression in individuals with and without alcohol use disorder. Data analyses are ongoing. Comparison of personality measures between individuals with alcohol dependence, regular alcohol use and no alcohol use. Data analyses are ongoing. Evaluation of the relationships between craving and alcohol use disorder, sleep, pain, social support and co morbid axis-1 diagnosis. Data analyses are ongoing. Decision making differences and alcohol use severity: the relationship between delay discounting and risky drinking. Data analyses are ongoing. The role of EF-hand domain family member D2 (EFHD2) in alcohol use disorder relevance for individuals exhibiting sensation-seeking behavior. Data analyses are ongoing. Analysis of protein kinase, cGMP-dependent, type I (PRKG1) variation in stress experience and alcohol use disorder. Data analyses are ongoing. VI. Other Progress During the reporting year, a collaboration was esablished with the Psychiatric Genetics Consortium (PGC), and data from the NIAAA Repository/Screening Database including large-scale genomic data and alcohol dependence diagnosis were shared with the consortium.

截至本报告，NIAAA 存储库/筛选数据库包含超过 2300 名个体的表型和/或基因组数据。表型数据包括精神病学诊断、许多与酒精相关的评估和测量，包括一生和最近的饮酒和酒精反应表型、个性和冲动测量、抑郁和焦虑症状、当前和早期的生活压力和创伤、攻击性、自杀性、吸烟、智商、睡眠质量、疼痛和整体生活质量。还提供实验室/生化测量。基因组数据包括通过 OCD 临床核心实验室和神经遗传学实验室 (NIAAA) 合作使用 Illumina 阵列进行的大规模单核苷酸多态性 (SNP) 基因分型。 鼓励所有 NIAAA PI 提交数据请求，以便使用共享的 NIAAA 存储库/筛选数据库进行研究项目和分析。记录项目并跟踪从最初请求到手稿出版的状态。此外，人类和基因组数据通过 BTRIS 和其他机制共享，包括与 NIH 支持的联盟（PGC 酒精中毒、ENIGMA）合作以确保数据共享。 酒精反应标准化评估（迷你酒精筛查检查 -MASE）、成瘾周期中的神经生物学变化（成瘾神经临床评估 -ANA）以及成瘾测量的开发正在通过自然史方案以及强迫症神经影像学核心的神经影像学研究进行中（PI，礼萨·莫梅南）。使用临床数据库，进行因素和路径分析，以确定 AUD 患者中在病因学和临床结果方面均存在异质性的因素和临床亚组。 一、近一年内发表论文的项目 成瘾神经临床评估的发展已发表两篇出版物。 合并和不合并创伤后应激障碍 (PTSD) 的酗酒住院患者的特征和临床结果比较 脂肪酸酰胺水解酶（FAAH）遗传变异和酒精相关结果以及酒精依赖严重程度的影响 研究前饥饿素原基因 Leu72Met 多态性在酒精依赖和酒精相关行为中的作用 性别、饮酒史和脂肪酸对重度饮酒酒精依赖住院患者肝损伤的影响 FAAH 遗传变异、焦虑和大脑对负面刺激的酒精依赖共病 PTSD 住院患者的反应 囊泡单胺转运蛋白 1 (VMAT1/SLC18A1) 基因遗传变异对酒精戒断严重程度的影响 酗酒和酒精相关表型中促肾上腺皮质激素释放因子结合蛋白（CRF-BP）的遗传变异 寻求治疗与不寻求治疗的酒精依赖个体的特征和临床结果的比较 与肥胖相关的肝脏、脂质和遗传因素及其与酒精依赖的关系 评估蒙哥马利-阿斯伯格抑郁量表 (MADRS) 在识别酒精依赖住院患者抑郁诊断方面的有效性 二.过去一年内提交手稿或在媒体上发表的项目 报告年度内，有三篇手稿提交和/或接受在同行评审期刊上发表，这些手稿是使用 NIAAA 存储库/筛选数据库的研究项目的结果。这些项目包括： 前蛋白转化酶枯草杆菌蛋白酶/kexin 9 (PCSK9) 的遗传变异和失调在酒精中毒和酒精相关表型中的作用 冲动介导成人注意力缺陷多动症状与酒精依赖严重程度的关系 研究分化簇 38 (CD38) rs3796863 多态性在酒精和金钱奖励中的作用：可能涉及多巴胺信号传导 三．正在准备手稿的项目 有六个项目正在准备手稿： 早期生活压力与酗酒住院患者的自杀有关 食欲素（下丘脑分泌素）受体 2 基因多态性 Val308Ile 对酒精依赖受试者的酒精依赖严重程度和应激反应的影响。 GATA结合蛋白4（GATA4）遗传变异与酒精使用障碍的关联分析 酒精使用障碍中多巴胺转运蛋白（DAT）的遗传学和表观遗传学 强迫性渴望是酒精依赖住院患者自杀意念的预测因子 使用当前 NIAAA 筛查协议中的措施对成瘾神经临床评估 (ANA) 领域进行评估 四．正在进行的项目仍在进行中 去年仍有四个项目仍在进行中： GABA（GABBR1 和 GABBR2）和 GABA 转运蛋白 1 (GAT1) 在酗酒和酒精相关表型中的遗传变异。数据分析正在进行中。 DCC netrin 1 受体 (DCC) 和突触核蛋白 α (SNCA) 基因之间的关联以及酒精患者和对照者冲动行为的测量。数据分析正在进行中。 血清/糖皮质激素调节激酶 1 (SGK1) 的遗传变异以及酒精使用障碍的相关临床表型。数据分析正在进行中。 低戒断率和高戒断率的酒精住院患者的外显子组测序。测序正在进行中。 五、一年来新开工项目 报告年度启动了十一个新的研究项目： 酒精中毒中加压素和加压素受体的遗传学。数据分析正在进行中。 C-反应蛋白在酒精使用障碍中的作用。数据分析正在进行中。 食欲激素、瘦素和胰淀素的游离肽和受体基因型，及其与酒精相关表型的关联。 数据分析正在进行中。 钙作为酒精使用障碍和阿坎酸反应的调节剂。 数据分析正在进行中。 GWAS 和外化行为的路径知情分析。 数据分析正在进行中。 葡萄糖和胰岛素信号的性别差异及其与患有和不患有酒精使用障碍的个体的攻击行为的关联。 数据分析正在进行中。 酒精依赖者、经常饮酒者和不饮酒者之间的人格测量比较。 数据分析正在进行中。 评估渴望与酒精使用障碍、睡眠、疼痛、社会支持和共病 axis-1 诊断之间的关系。数据分析正在进行中。 决策差异和饮酒严重程度：延迟折扣和危险饮酒之间的关系。 数据分析正在进行中。 EF 手域家族成员 D2 (EFHD2) 在酒精使用障碍中的作用与表现出感觉寻求行为的个体相关。 数据分析正在进行中。 压力体验和酒精使用障碍中蛋白激酶、cGMP 依赖性 I 型 (PRKG1) 变异的分析。 数据分析正在进行中。 六． 其他进展 在报告年度内，与精神病遗传学联盟 (PGC) 建立了合作，并与该联盟共享了 NIAAA 存储库/筛查数据库的数据，包括大规模基因组数据和酒精依赖诊断。