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

基本信息

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
项目类别：
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

项目摘要

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 Anotia/Microtia是一种出生缺陷，其特征是缺乏或发育不全的外耳；据估计 > 80,000名美国人生活在这种情况下，> 75％的受影响个人。这项研究将确定Anotia/Microtia的社会/环境和遗传驱动因素，强调解决西班牙裔/拉丁人种群的健康差异。值得注意的是，出生率相对于非西班牙裔白人种群，西班牙裔厌食症/小阶级有所增加，但西班牙裔婴儿较少可能被诊断出患有厌氧/微图综合症，而不是其非西班牙裔白人同伴。这项研究会使用三部分的方法。首先，通过利用> 1000万活产和> 3500例的数据基于人群的先天缺陷的Anotia/Microtia在加利福尼亚和德克萨斯州的注册处，它将评估社会人口统计学因素解释了厌氧/小综合症的出生率的差异在西班牙裔和非西班牙裔人口之间。第二，使用祖先感知的全基因组关联方法（拖拉机），加利福尼亚生物库计划的存档生物测量和国家出生缺陷预防研究，以及来自Gabriella Miller儿童的公开可用的全基因组测序数据小儿研究计划，它将确定与西班牙裔和厌食症相关的遗传变异非西班牙裔人。接下来，它将将严格的机器学习技术应用于国家的数据先天缺陷的预防研究（n = 699例厌食/小落级病例，> 10,000个没有出生缺陷的对照）确定与西班牙裔和非西班牙裔人群中与Anotia/Microtia相关的孕产妇暴露。最后，它将对社会人口统计学，遗传和母体因素的作用进行综合评估。在确定Anotia/Microtia的风险时。在实现这些目标时，研究将：确定西班牙裔人群中Anotia/Microtia的差异；阐明了Anotia/Microtia的病因通过表征与这种疾病相关的遗传变异的不同种群，这将成为目标未来的调查；并确定可用于促进的潜在可修改的母亲暴露预防。