NIAAA Repository/Screening Database Management and Research

截至本报告，NIAAA知识库/筛选数据库包括2900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 2900 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 (6) resulting in manuscripts published within the past year: Obsessive craving as a predictor of suicidal ideation in alcohol dependent inpatients Effects of TSPO genotype on perceived stress, anxiety, and alcohol drinking behavior Impaired control, suggestibility and alcohol-related outcomes (2 publications) Genetics and epigenetics of the dopamine transporter (DAT) in alcohol use disorder (2 publications) Genome wide association studies of the Self-Rating of Effects of Ethanol (SRE) (external collaboration) Shared genetic risk between eating disorder- and substance-use-related phenotypes (external collaboration) II. Projects (2) resulting in manuscript submissions, revisions, or publications in press, within the past year: Effects of the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile on severity of alcohol dependence and stress response in alcohol-dependent subjects Phenotypic and genotypic relationships characterizing type and severity of alcohol use responses III. Projects (12) with manuscripts in preparation: Neurofunctional domains in alcohol use disorder predict multiple adverse outcomes linked to addiction Reporting of adverse childhood events as a function of race/ethnicity and gender and their influence on drinking behaviors Free peptide and receptor genotype of the appetitive hormones, leptin and amylin, and their association with alcohol-related phenotypes Predictive value of anxiety scales in alcohol dependent patients Binge drinking behavior as a function of risk factors for alcohol use disorder (2 manuscripts) 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 The role of C-Reactive protein in alcohol use disorder An imaging genetics study of the prepro-ghrelin and glucagon-like peptide-1 receptor gene variants in alcohol use disorder Electrocardiogram and other cardiovascular indicators of at-risk alcohol drinking Role of circadian and cannabinoid genes in Sleep and AUD An Investigation into the Role of Metabolic Biomarkers in the Anticipation of Reward in Treatment Seeking Alcoholics The relationship between CNR1 polymorphisms and alcohol abuse IV. Ongoing projects (11) still in progress: GABA (GABBR1 and GABBR2) and GABA transporter 1 (GAT1) genetic variation in alcoholism and alcohol-related phenotypes. 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, additional sequencing is in progress, data analyses are ongoing. Association between LRRK2 gene and compulsive behavior in alcoholic patients. 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. 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. Connor-Davidson Resilience Scale (CDRS): association with childhood trauma, alcohol-related outcomes and psychopathology. Data analyses in progress. Phenotypic differences in reward, pain, and negative affect measures in individuals with genetic variation in expression of OPRM1. Data analyses are ongoing. Association between FXYD2 and DRD2 genes and measures related to dopamine signaling in alcohol use disorder. Data analyses are ongoing. V. New projects (13) initiated within the past year: An evaluation of binge drinking definitions and measurement: assessing the importance of consumption duration Phenotypic and genotypic relationships between EKG markers and alcohol use responses Vital signs and circadian relationships to alcohol use responses Genetic variations in alcohol metabolism genes and alcohol-related phenotypes Analysis of weight trends and micronutrient stores in patients admitted to an inpatient alcohol rehabilitation program Association of amygdalar genes to negative emotionality in AUD and other addictive disorders Thyroid hormones, impulsivity, and severity of alcohol dependence Immunoglobulin levels in alcohol use disorder and their association with comorbid major depressive disorder and chronic stress Nicotinic alpha subunit effects on personality using confirmatory factor analysis Inflammation, iron loading, and sleep quality in AUD Genetic variance in the aquaporin gene and sleep quality in AUD Neurological predictors of relapse in alcohol use disorder Association of delayed reward discounting performance with dopaminergic gene variation in individuals across the spectrum of alcohol use and alcohol use disorder VI. Other Progress As a result of an established collaboration with the Psychiatric Genetics Consortium (PGC), a manuscript was published including data from the NIAAA Repository/Screening Database looking at shared genetic risk of substance use and eating disorder phenotypes. As a result of an established collaboration with Indiana University and the Centenary Institute in Australia, a manuscript was published including data from the NIAAA Repository/Screening Database, looking at genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations. A new collaboration was established with The Alcoholic Hepatitis Network project (AlcHepNet) to share data relevant to investigations of new treatments in alcoholic hepatitis.