Leveraging Ethnic Anotia-microtia Disparities for Discovery (LEADD) Study

利用民族小耳症差异进行发现 (LEADD) 研究

• 批准号: 10715649
• 负责人: Jeremy Schraw
• 金额: $ 79.37万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-31 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715649
• 关键词: Address; Adverse event; Affect; American; Amerindian; Anxiety; Archives; Awareness; Birth; Blood; California; Characteristics; Child; Clinical Management; Confidence Intervals; Congenital Abnormality; Data; Diagnosis; Diet; Disease; Disparity; Ear; Education; Environment; Environmental Risk Factor; Epidemiology; Ethnic Origin; Ethnic Population; Etiology; External Ear; Facial nerve structure; Future; Genes; Genetic; Genetic Variation; Genome; Genotype; Health Care Costs; Hearing; Heritability; Hispanic; Hispanic Populations; Human Genetics; Individual; Infant; Investigation; Latinx population; Life Cycle Stages; Live Birth; Machine Learning; Maps; Maternal Exposure; Maternal Health; Mental Depression; Methods; Monitor; Mothers; Neighborhoods; Neonatal; Not Hispanic or Latino; Operative Surgical Procedures; Participant; Patient Self-Report; Pediatric Research; Pharmaceutical Preparations; Population; Population Heterogeneity; Prevalence; Prevention; Primary Prevention; Reconstructive Surgical Procedures; Registries; Risk; Risk Estimate; Risk Factors; Role; Socioeconomic Factors; Socioeconomic Status; Spottings; Syndrome; Techniques; Texas; Time; Update; Validation; Work; adverse outcome; biobank; bioinformatics tool; biological specimen archives; case control; causal variant; childhood hearing loss; congenital anomaly; ethnic difference; ethnic disparity; forest; genetic variant; genome sequencing; genome wide association study; genome-wide; health disparity; hearing impairment; high risk population; insight; member; microtia; multi-ethnic; multidisciplinary; non-genetic; novel; peer; population based; programs; residence; segregation; social; sociodemographic factors; sociodemographics; whole genome

PROJECT SUMMARY Anotia/microtia is a birth defect characterized by an absent or hypoplastic external ear; it is estimated that >80,000 Americans are living with this condition, which causes significant hearing loss in >75% of affected individuals. This study will identify social/environmental and genetic drivers of anotia/microtia, with an emphasis on addressing health disparities for Hispanic/Latinx populations. Notably, the birth prevalence of anotia/microtia is increased in Hispanic relative to non-Hispanic white populations, but Hispanic infants are less likely to be diagnosed with an anotia/microtia syndrome than their non-Hispanic white peers. This study will use a three-part approach. First, by leveraging data on >10 million live births and >3,500 cases with anotia/microtia from population-based birth defects registries in California and Texas, it will evaluate the extent to which sociodemographic factors explain differences in the birth prevalence of anotia/microtia syndromes between Hispanic and non-Hispanic populations. Second, using an ancestry-aware genome-wide association method (Tractor), archived biospecimens from the California Biobank Program and National Birth Defects Prevention Study, and publicly available whole-genome sequencing data from the Gabriella Miller Kids First Pediatric Research Initiative, it will identify genetic variants associated with anotia/microtia in Hispanic and non-Hispanic individuals. Next, it will apply a rigorous machine learning technique to data from the National Birth Defects Prevention Study (N=699 cases with anotia/microtia and >10,000 controls without birth defects) to identify maternal exposures associated with anotia/microtia in Hispanic and non-Hispanic populations. Finally, it will perform an integrative assessment of the role of sociodemographic, genetic, and maternal factors in determining risk for anotia/microtia. In accomplishing these objectives, the study will: identify drivers of disparities in anotia/microtia among Hispanic populations; shed light on the etiology of anotia/microtia in diverse populations by characterizing genetic variants associated with this disease, which will be targets for future investigation; and identify potentially modifiable maternal exposures that could be used to facilitate prevention.

项目摘要 无耳症/小耳症是一种出生缺陷，其特征是外耳缺失或发育不全;据估计， 超过80，000名美国人患有这种疾病，导致超过75%的受影响者严重听力损失。 个体这项研究将确定无耳症/小耳症的社会/环境和遗传驱动因素， 强调解决西班牙裔/拉丁裔人口的健康差距。值得注意的是， 与非西班牙裔白色人群相比，西班牙裔婴儿的无耳症/小耳症增加，但西班牙裔婴儿的无耳症/小耳症减少。 比非西班牙裔白色同龄人更有可能被诊断为无耳症/小耳症综合征。本研究将 使用三部分方法。首先，通过利用超过1000万例活产和超过3,500例 根据加州和德克萨斯州基于人口的出生缺陷登记处的无耳症/小耳症，它将评估 社会人口学因素解释了无耳/小耳综合征出生患病率的差异 西班牙裔和非西班牙裔之间的差异第二，使用具有祖先意识的全基因组关联， 方法（拖拉机），来自加州生物样本库计划和国家出生缺陷的存档生物标本 预防研究，以及来自加布里埃拉米勒儿童第一的公开可用的全基因组测序数据 儿科研究倡议，它将确定遗传变异与无耳/小耳在西班牙裔和 非西班牙裔人士。接下来，它将应用严格的机器学习技术来处理来自国家统计局的数据。 出生缺陷预防研究（N=699例无耳/小耳病例和> 10，000例无出生缺陷的对照） 确定西班牙裔和非西班牙裔人群中与无耳症/小耳症相关的母体暴露。 最后，它将对社会人口学、遗传和母亲因素的作用进行综合评估 在确定无耳症/小耳症的风险。为实现这些目标，研究将： 西班牙裔人群中无耳症/小耳症的差异; 通过表征与这种疾病相关的遗传变异，这将是目标， 未来的调查;并确定潜在的可改变的母亲暴露，可用于促进 预防