Eating Disorders Genetics Initiative (EDGI)

饮食失调遗传学倡议 (EDGI)

• 批准号: 10425368
• 负责人: CYNTHIA M BULIK
• 金额: $ 128.33万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-11 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425368
• 关键词: Affect; Anorexia Nervosa; Australia; Beds; Behavior; Behavior Disorders; Binge Eating; Binge eating disorder; Biology; Birth; Body mass index; Bulimia; Clinical; Data; Data Set; Denmark; Deposition; Desire for food; Dimensions; Disease; Eating Disorders; Environment; Environmental Risk Factor; Epidemiology; Etiology; Foundations; Funding; Genes; Genetic; Genetic Diseases; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Genomics; Genotype; Goals; Heritability; Heterogeneity; Individual; Joints; Legal; Link; Mendelian randomization; Mental disorders; Meta-Analysis; Metabolic; Metabolic Diseases; Modeling; Morbidity - disease rate; National Institute of Mental Health; Nature; New Zealand; Outcome; Participant; Personality; Phenotype; Physical activity; Polygenic Traits; Population Registers; Psychopathology; Quality of life; Recontacts; Records; Research; Risk; Sampling; Shapes; Testing; Therapeutic; Treatment outcome; Vomiting; Work; advanced analytics; base; comorbidity; disorder risk; excessive exercise; genetic analysis; genetic architecture; genetic association; genome wide association study; genome-wide; health care service utilization; improved; insight; mortality; pleiotropism; psychiatric comorbidity; psychiatric genomics; recruit; statistics; trait; treatment response; working group

Project Summary We propose the Eating Disorders Genetics Initiative (EDGI) to rapidly and efficiently advance genomic discovery across the three major eating disorders (EDs) [AN (anorexia nervosa), BN (bulimia nervosa), and BED (binge-eating disorder)]. We propose a testable conceptualization of EDs as arising from a shared genetic vulnerability to a core trait (e.g., dysregulated appetite) that is further differentiated across clinical presentations of AN, BN, and/or BED by differing genetic predispositions to dimensional ED behaviors (e.g., binge eating, vomiting, excessive exercise), BMI, personality, comorbid psychopathology, physical activity, and metabolic traits. We propose that this palette of genetic risk is further influenced by environmental factors that affect emergence, course, and outcome of the ED. EDGI will empirically test and refine this model. Importantly, we will ascertain ancestrally diverse cases reflecting known epidemiological distributions of EDs. Using an efficient online ascertainment approach, EDGI will: (Aim 1) obtain deep phenotyping on course of illness, comorbid psychiatric conditions, treatment response, healthcare utilization, and quality of life on ~4000 participants in the Anorexia Nervosa Genetics Initiative (ANGI) from the US, Australia (AUS), and New Zealand (NZ); (Aim 2) ascertain, phenotype, and genotype 4500 new AN cases [(US, AUS, NZ, and Denmark (DK; identified in national records an genotypes from PKU cards from birth)]; ~5950 BN cases (US, AUS, NZ, DK); ~4050 BED cases (US, AUS, NZ) and 1500 controls; (Aim 3) conduct pre-planned genome-wide association studies (GWAS) for AN, BN, BED, any ED, and component behaviors, with external replications with Swedish and Icelandic data, plus a specific set of post-GWAS analyses; (Aim 4) apply advanced analytic strategies to test and refine our etiological model of EDs to explicate within-ED heterogeneity, explore the genetic relation between EDs and a broad array of psychiatric, metabolic, anthropometric, physical activity, educational phenotypes and the forces that shape those relationships, and preliminarily explore polygenic risk (PRS) x environmental interactions. EDGI represents the next logical step in ED genomics. Our scientific team recently completed ANGI, yielding compelling genetic findings for AN including the identification of 8 significant loci and intriguing genetic correlations with both psychiatric and metabolic traits strongly suggesting that AN is a metabo-psychiatric disorder. EDGI will expand to include BN and BED. Deliverables include: (a) rich phenotypic and genotypic data on large AN, BN, and BED samples; (b) clarification of the nature of genetic relationship among EDs and between EDs and other target traits; (c) an empirical model of ED risk and differentiation; (d) preliminary insight into how genes and environment interact in EDs; (e) sample and data deposit per current legal and regulatory standards and publicly available summary statistics. Our ultimate goal aligns with the Psychiatric Genomics Consortium (PGC) by delivering “actionable” findings that will be transformable into biologically, clinically, and therapeutically meaningful insights on EDs.

项目摘要 我们提出饮食失调遗传学倡议(EDGI)，以快速有效地推进基因组学 发现了三种主要的饮食失调(EDs)[AN(神经性厌食症)，BN(神经性暴食症)，和 床(暴食症)]。我们提出了一种可测试的EDS概念，认为它源于共享的基因 易患一种核心特征(例如，食欲失调)，并在临床表现中进一步区分 通过不同的维度ED行为的遗传倾向(例如，暴饮暴食， 呕吐、过度运动)、体重指数、个性、共病精神病、体力活动和代谢 特征。我们认为，这种遗传风险的调色板进一步受到环境因素的影响，这些因素影响 勃起功能障碍的产生、过程和结局。Edgi将对这一模型进行实证测试和改进。重要的是，我们 将确定反映已知EDS流行病学分布的祖传不同病例。 使用有效的在线确定方法，Edgi将：(目标1)在以下过程中获得深入的表型 疾病、并存精神疾病、治疗反应、医疗保健利用和生活质量 来自美国、澳大利亚和新西兰的Nervosa厌食症遗传学倡议(ANGI)的参与者 (新西兰)；(目标2)确定4500例新的AN病例的表型和基因型[(美国、澳大利亚、新西兰和丹麦(DK； 国家记录中从出生起从PKU卡中确定的基因类型)]；约5950例BN病例(美国、澳大利亚、新西兰、朝鲜)； 约4050例卧床病例(美国、澳大利亚、新西兰)和1500例对照；(目标3)进行预先计划的全基因组关联 对AN、BN、BED、任何ED和组件行为的研究(GWAS)，与瑞典语进行外部复制 和冰岛的数据，外加一套具体的地理信息系统后分析；(目标4)应用先进的分析战略 测试和完善我们的EDS病因模型，以解释ED内的异质性，探索遗传关系 在EDS和一系列精神病学、新陈代谢、人体测量学、体力活动、教育 表型和塑造这些关系的力量，并初步探索多基因风险(Prs)x 环境相互作用。Edgi代表了ED基因组学的下一个合乎逻辑的步骤。 我们的科学团队最近完成了ANGI，为包括 8个与精神和代谢性状相关的显著基因座和有趣的遗传相关性 强烈表明AN是一种后天精神障碍。EDGI将扩大到包括国阵和Bed。 可交付成果包括：(A)大量AN、BN和床样本的丰富表型和基因数据；(B) 澄清遗传标记之间以及标记标记与其他目标性状之间的遗传关系的性质；(C) ED风险和分化的经验模型；(D)基因和环境如何相互作用的初步洞察 电子数据系统；(E)按照现行法律和法规标准进行样本和数据存放，并向公众提供摘要 统计数据。我们的最终目标与精神病学基因组联盟(PGC)保持一致，通过提供“可操作的” 这些发现将转化为对ED有生物学、临床和治疗意义的见解。