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

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

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.