Genetic Architecture of Avoidant/Restrictive Food Intake Disorder

回避/限制性食物摄入障碍的遗传结构

• 批准号: 10684064
• 负责人: CYNTHIA M BULIK
• 金额: $ 74.24万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-16 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10684064
• 关键词: Acceleration; Adult; Anorexia Nervosa; Anxiety; Architecture; Binge eating disorder; Biology; Bulimia; Categories; Child; Chromosome Mapping; Collection; DNA; DSM-V; Data; Data Set; Desire for food; Development; Diagnostic; Disease; Dissection; Eating Disorders; Etiology; Functional disorder; Genetic; Genetic Diseases; Genetic Research; Genetic study; Genomics; Genotype; Heritability; Home; Infrastructure; Interview; Investigation; Joints; Life; Maps; Medical; Mendelian randomization; Mental disorders; Meta-Analysis; Metabolic; Methodology; Nature; Nutritional; Outcome; Parents; Pharmaceutical Preparations; Pharmacogenomics; Pharmacological Treatment; Phenotype; Prevention; Research; Resources; Risk; Sampling; Sensory; Taxes; Testing; Work; advanced analytics; autism spectrum disorder; avoidant restrictive food intake disorder; disease classification; feeding; food avoidance; food restriction; genetic architecture; genetic association; genetic information; genome wide association study; genome-wide; interest; operation; pleiotropism; polygenic risk score; psychiatric genomics; psychosocial; saliva sample; therapy development; trait; working group

Project Summary We propose to rapidly accelerate our understanding of the biology of eating disorders by conducting the first genomic study of avoidant/restrictive food intake disorder (ARFID): ARFID-GEN. ARFID, first included in the DSM-5 Feeding and Eating Disorders chapter in 2013, is characterized by food avoidance or restriction due to three non-mutually exclusive presentations (1) phobic avoidance, (2) sensory sensitivity, or (3) disinterest/low appetite. Little is known about risk mechanisms and pathophysiology of ARFID, and no genetic studies have been conducted to date. Ongoing is the Eating Disorders Genetic Initiative (EDGI; R01MH120170), aimed to further the genomic discovery of the eating disorders: anorexia nervosa, bulimia nervosa, and binge-eating disorder. Absent from EDGI is the serious, taxing, and potentially life-threatening ARFID. We propose an efficient genomic analysis of ARFID, by leveraging EDGI operations and resources to conduct the first genome-wide association study (GWAS) of ARFID. Moreover, by combining ARFID with EDGI, we will achieve a complete explication of the DSM-5 feeding and eating disorders chapter. Conceptually, our proposal will test whether ARFID shares a core set of genetic factors with other eating disorders yet is differentiated by a set of disorder-specific genetic factors. Using an efficient and economical approach, ARFID-GEN will: (Aim 1) collect 5,000 ARFID cases and 1,000 new child controls with phenotype and genotype information; (Aim 2) conduct the first GWAS of ARFID plus a standard set of post-GWAS analyses in order to reveal the genetic architecture of ARFID; (Aim 3) apply advanced analytic strategies to explicate the common and divergent genomic architecture of ARFID and the other eating disorders; and (Aim 4) explore the genomic relation among ARFID and multiple psychiatric, metabolic, and anthropometric traits. Launching ARFID-GEN now is the next logical step in eating disorder genomics. Our team has been at the forefront of eating disorder genetics research. Deliverables of the proposed specific aims include: (a) Analysis-ready deep phenotypic and genotypic datasets from the largest ARFID collection in the word; (b) ARFID GWAS; (c) defining the genetic relation of ARFID with other eating disorders; (d) genetic assessment of ARFID’s relation to other phenotypes, informing and refining etiology. The proposed aims will not only reveal the underlying genomic architecture of ARFID, but combined with other ongoing studies and existing data, fully explicate the feeding and eating disorders chapter of the DSM-5, affording the development of a genetically-informed nosology. Given pharmacological treatments for all eating disorders are lacking, we will have created a complete map of the genomics of ARFID, and the eating disorders, that will open avenues for pharmacogenomics and the repurposing and development of medications that target disease biology.

项目摘要 我们建议通过进行第一个 回避/限制性食品摄入障碍（ARFID）的基因组研究：Arfid-gen。 arfid，首先包括 DSM-5喂养和饮食失调术在2013年的一章，其特征是避免食物或限制 三个非纯正的排斥演示（1）避免恐惧症，（2）感官敏感性，或（3）无趣/低 食欲。关于ARFID的风险机制和病理生理学知之甚少，没有遗传研究 是迄今为止进行的。正在进行的是饮食失调的遗传倡议（EDGI； R01MH120170），目的是 此外，饮食失调的基因组发现：厌食 紊乱。 EDGI缺乏是严重的，征税且潜在的威胁生命的Arfid。我们提出了一个 通过利用EDGI操作和资源进行第一个，对ARFID进行有效的基因组分析 Arfid的全基因组关联研究（GWAS）。而且，通过将Arfid与Edgi结合在一起，我们将实现 DSM-5喂养和饮食失调片章的完整说明。从概念上讲，我们的建议将测试 Arfid是否与其他饮食失调共享一组遗传因素的核心 特异性遗传因素。 使用高效和经济的方法，Arfid-Gen将：（目标1）收集5,000个Arfid案件和1,000个 具有表型和基因型信息的新儿童控制； （AIM 2）进行Arfid和A的第一个GWA 为了揭示Arfid的遗传结构，标准的GWAS后分析集； （目标3）申请 先进的分析策略，以阐明Arfid的常见和不同的基因组结构 其他饮食失调； （AIM 4）探索Arfid和多种精神病学之间的基因组关系， 代谢和人体测量特征。现在推出Arfid-Gen是饮食失调症的下一个逻辑步骤 基因组学。 我们的团队一直处于饮食失调遗传学研究的最前沿。提议的特定的可交付成果 目的包括：（a）从最大的ARFID集合中的分析的深层表型和基因型数据集 这个词； （b）Arfid GWAS； （c）定义ARFID与其他饮食失调的遗传关系； （d）遗传 评估Arfid与其他表型的关系，告知和精炼病因。拟议的目标将 不仅揭示了ARFID的基因组建筑，而且还与其他正在进行的研究相结合 现有数据，充分阐述了DSM-5的喂养和饮食失调片章节，提供了开发 遗传信息的疾病。鉴于缺乏所有饮食失调的药物治疗，我们 将创建一张ARFID基因组和饮食失调的完整地图，这将开放途径 用于药物基因组学以及针对疾病生物学的药物的重新利用和开发。