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: 10625586
• 负责人: CYNTHIA M BULIK
• 金额: $ 75.79万
• 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/10625586
• 关键词: Adult; Anorexia Nervosa; Anxiety; Architecture; Binge eating disorder; Biology; Bulimia; Categories; Child; 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; base; 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.

项目概要 我们建议通过进行首次研究来快速加速我们对饮食失调生物学的理解 回避/限制性食物摄入障碍（ARFID）的基因组研究：ARFID-GEN。 ARFID，首先被纳入 2013 年 DSM-5 喂养和饮食失调章节，其特点是由于以下原因而避免或限制食物： 三种非互斥的表现（1）恐惧性回避，（2）感官敏感性，或（3）不感兴趣/低 食欲。人们对 ARFID 的风险机制和病理生理学知之甚少，也没有任何遗传学研究表明 迄今已进行。正在进行的饮食失调基因计划（EDGI；R01MH120170）旨在 进一步发现饮食失调的基因组：神经性厌食症、神经性贪食症和暴食症 紊乱。 EDGI 中缺少严重、繁重且可能危及生命的 ARFID。我们提出一个 通过利用 EDGI 运营和资源进行首次 ARFID 高效基因组分析 ARFID 的全基因组关联研究（GWAS）。此外，通过将ARFID与EDGI相结合，我们将实现 DSM-5 喂养和饮食失调章节的完整说明。从概念上讲，我们的提案将测试 ARFID 是否与其他饮食失调共享一组核心遗传因素，但又通过一组 疾病特异性遗传因素。 使用高效且经济的方法，ARFID-GEN 将：（目标 1）收集 5,000 个 ARFID 案例和 1,000 个 具有表型和基因型信息的新子对照； （目标 2）进行 ARFID 的首次 GWAS 以及 GWAS 后分析的标准集，以揭示 ARFID 的遗传架构； （目标 3）申请 先进的分析策略来解释 ARFID 的共同和不同的基因组结构以及 other eating disorders; （目标 4）探索 ARFID 与多种精神疾病之间的基因组关系， 代谢和人体测量特征。现在推出 ARFID-GEN 是解决饮食失调问题的下一个合乎逻辑的步骤 基因组学。 我们的团队一直处于饮食失调遗传学研究的前沿。拟议具体的交付成果 目标包括： (a) 来自最大的 ARFID 集合的分析就绪的深层表型和基因型数据集 这个词； (b) ARFID GWAS； (c) 界定 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，了解并完善病因学。拟议的目标将 不仅揭示了 ARFID 的底层基因组架构，而且结合其他正在进行的研究 现有数据，充分阐明DSM-5的喂养和饮食失调章节，为开发提供依据 遗传信息的疾病分类学。鉴于缺乏针对所有饮食失调的药物治疗，我们 将创建 ARFID 基因组学和饮食失调的完整图谱，这将开辟道路 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。