NIAAA Repository/Screening Database Management and Research

截至本报告，NIAAA知识库/筛选数据库包括2700多个个体的表型和/或基因组数据。表型数据包括精神病诊断、各种酒精相关的评估和测量，包括终生和近期消费和酒精反应表型、个性和冲动测量、抑郁和焦虑症状、当前和早期生活压力和创伤、攻击、自杀、吸烟、智商、睡眠质量、疼痛和整体生活质量。实验室/生化测量也可用。基因组数据包括：1)使用Illumina阵列进行大规模单核苷酸多态性（SNP）基因分型；2)通过OCD临床核心实验室和神经遗传学实验室（NIAAA）的合作，对一部分受试者进行外显子组测序。

As of this report, the NIAAA Repository/Screening Database includes phenotype and/or genomic data on more than 2700 individuals. Phenotype data include psychiatric diagnoses, a variety 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 1) large-scale single nucleotide polymorphism (SNP) genotyping performed using Illumina arrays, and 2) exome sequencing of a subset of subjects, both via a partnership between the Clinical Core Laboratory of the OCD, and the Laboratory of Neurogenetics (NIAAA). All NIAAA PIs 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. I. Projects (9) resulting in manuscripts published within the past year: A role for the CD38 rs3796863 polymorphism in alcohol and monetary reward Effect of alcohol use disorder on cellular aging/telomere length Genome wide association studies of the Self-Rating of Effects of Ethanol (SRE) (external collaboration) Association of high-intensity binge drinking with lipid and liver function enzyme levels The relationship between delay discounting and alcohol dependence in individuals with and without comorbid psychopathology. Assessment of Addictions Neuroclinical Assessment (ANA) domains using measures from the current NIAAA screening protocol Stress vulnerability and alcohol use and consequences: from human laboratory studies to clinical outcomes DNA methylation age is accelerated in alcohol dependence Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders (external collaboration) II. Projects (6) resulting in manuscript submissions, revisions, or publications in press, within the past year: Sex, clinical outcomes, and neurofunctional domains in alcohol use disorder Obsessive craving as a predictor of suicidal ideation in alcohol dependent inpatients Effects of TSPO genotype on perceived stress, anxiety, and alcohol drinking behavior Genetic variation in FKBP5 influences cortisol levels in individuals with alcohol use disorder Elevated stearoyl-CoA desaturase 1 activity is associated with alcoholic liver disease Effects of the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile on severity of alcohol dependence and stress response in alcohol-dependent subjects. III. Projects (4) with manuscripts in preparation: Reporting of adverse childhood events as a function of race/ethnicity and gender and their influence on drinking behaviors Binge drinking behavior as a function of risk factors for alcohol use disorder Role of current stress and perceived stress in alcohol-dependence severity and quality of life: an update to the study of childhood trauma in alcohol use disorder Genetics and epigenetics of the dopamine transporter (DAT) in alcohol use disorder IV. Ongoing projects (18) still in progress: 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. Comparison of resting state functional connectivity, alcohol consumption patterns, and CASE behavior as a function of CHRNA5 genotype. Data analyses are ongoing Exome sequencing of alcoholic inpatients with low and high withdrawal. Initial sequencing is complete, data analyses are ongoing. 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. GWAS and pathway-informed analysis of externalizing behaviors. Data analyses are ongoing. Genetics of Alcohol Use Disorder with comorbid mood and anxiety disorders. Data analyses are ongoing. Electrocardiogram and other cardiovascular indicators of at-risk alcohol drinking. Data analyses are ongoing. Differences in withdrawal severity and craving in relation to successive detoxifications amongst treatment-seeking alcohol dependent Individuals. Data analyses are ongoing. Association between LRRK2 gene and compulsive behavior in alcoholic patients. Data analyses are ongoing. An imaging genetics study of the prepro-ghrelin and glucagon-like peptide-1 receptor gene variants in alcohol use disorder. Data analyses are ongoing. Neurobiological substrates of racial/ethnic disparity in alcohol use disorder: characterization of vulnerability/resilience via imaging, genetics, and biobehavioral information. Data analyses are ongoing. The relationship between CNR1 polymorphisms and alcohol abuse. Data analyses are ongoing. Characterization of drinking patterns in alcohol use disorder by Timeline Follow-Back variability analysis: association with craving, other substance use, psychopathology, and alcohol-related liver conditions. Data analyses are ongoing. Association between dopaminergic genetic variation and IV alcohol consumption in the lab and in the field. Data analyses are ongoing. PNPLA3, drinking behavior, and metabolic parameters in alcoholics. Data analyses are ongoing. V. New projects (7) initiated within the past year: Impaired Control, Suggestibility and Alcohol-Related Outcomes An Investigation into the Role of Metabolic Biomarkers in the Anticipation of Reward in Treatment Seeking Alcoholics Connor-Davidson Resilience Scale (CDRS): association with childhood trauma, alcohol-related outcomes and psychopathology Phenotypic differences in reward, pain, and negative affect measures in individuals with genetic variation in expression of OPRM1 VI. Other Progress As a result of the collaboration established last year with the Psychiatric Genetics Consortium (PGC), a manuscript was published including data from the NIAAA Repository/Screening Database, looking at genome-wide associations with alcohol use disorder. In collaboration with Indiana University and the Centenary Institute in Australia, a manuscript was published including data from the NIAAA Repository/Screening Database, looking at genetics of the self-rating effects of alcohol. A new collaboration is being established with The Alcoholic Hepatitis Network project (AlcHepNet) to share data relevant to investigations of new treatments in alcoholic hepatitis.