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

项目总结 厌食症/小耳症是一种出生缺陷，其特征是外耳缺失或发育不良；据估计 有8万美国人患有这种疾病，75%的患者会导致严重的听力损失 个人。这项研究将确定厌食症/小耳症的社会/环境和遗传驱动因素，以及 强调解决拉美裔/拉丁裔人口的健康差距问题。值得注意的是，婴儿的出生率 与非西班牙裔白人相比，西班牙裔婴儿的厌食症/小耳畸形较多，但西班牙裔婴儿较少 比他们的非西班牙裔白人同龄人更有可能被诊断为厌食症/小耳畸形综合征。这项研究将 使用三个部分的方法。首先，通过利用1000万活产儿和3500例新生儿的数据， 来自加利福尼亚州和得克萨斯州基于人口的出生缺陷登记的缺氧症/微小畸形，它将评估其程度 社会人口学因素对厌食症/小耳畸形综合征出生患病率差异的解释 西班牙裔和非西班牙裔人口之间的差距。第二，使用祖先意识的全基因组关联 方法(拖拉机)，加州生物库计划存档的生物样本和国家出生缺陷 预防研究，以及来自加布里埃拉·米勒儿童的公开的全基因组测序数据 儿科研究倡议，它将确定与西班牙裔和西班牙裔人的厌食症/小耳畸形相关的遗传变异 非西班牙裔个人。接下来，它将应用一种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例厌氧症/小儿麻痹症和&GT；10,000例无出生缺陷的对照) 确定与西班牙裔和非西班牙裔人群中的厌食症/小儿麻痹症相关的母亲暴露。 最后，它将对社会人口、遗传和母体因素的作用进行综合评估 在确定厌食症/小耳畸形的风险方面。在实现这些目标的过程中，研究将：确定 拉美裔人群中的厌食症/小耳畸形的差异；揭示了 通过表征与这种疾病相关的遗传变异来区分不同的人群，这将成为 未来的调查；并确定潜在的可改变的孕产妇接触情况，以促进 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.