CIDR: SEQUENCING SERVICES USING WHOLE GENOME SEQUENCING FOR NCI (AMOS),

CIDR：使用 NCI 全基因组测序的测序服务 (AMOS)，

• 批准号: 10949101
• 负责人: Kimberly F Doheny
• 金额: $ 86.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-11 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10949101
• 关键词: CIDR; SEQUENCING; SERVICES; USING; WHOLE

Lung cancer (LC) is the third most common cancer in the U.S. with African Americans (AAs) having the highest incidence and mortality. While previous linkage, admixture, whole-exome sequencing and genome-wide association studies in European-Americans and Asian ancestry show statistically compelling effects, much of LC heritability in AAs is yet to be explained. To date, no familial lung cancer (FLC) study has been explored in AAs. Genetic Epidemiology of Lung Cancer Consortium (GELCC) is the only consortium in the U.S. that studies FLC families, but to date, the majority of data collection and analyses are of European-Americans ancestry. Examining genetic FLC risk in AAs provides complementary data to localize susceptibility loci and DNA damage response and repair pathway genes because this population has different risk alleles, effect size, linkage patterns, and tobacco related exposures than is seen in more well-characterized racial/ethnic groups. We hypothesize that germline high-penetrance variants that are rare or low-frequency in global populations are enriched in high-risk FLC families among the AAs population. This supplemental project generates high-coverage whole-genome sequencing; utilizes publicly available whole-genome sequencing data for African population controls; and utilizes a family-based study design, ensuring we will detect people who carry rare and low-frequency variants of larger effect.

肺癌(LC)是美国第三大常见癌症，非洲裔美国人(AAs)的发病率最高， 死亡率。虽然先前在欧美和亚洲血统中进行的连锁、混合、全外显子组测序和全基因组关联研究显示了统计上令人信服的效果，但许多LC在AAS中的遗传性尚未得到解释。到目前为止，还没有家族性肺癌(FLC)的研究在AAS中被探索。肺癌遗传流行病学协会(GELCC)是美国唯一一个研究FLC家族的协会，但到目前为止， 大多数数据收集和分析都有欧洲裔美国人的血统。检测AAS的遗传FLC风险为定位易感基因和DNA损伤反应和修复途径基因提供了补充数据，因为与更具特征的种族/民族群体相比，该人群具有不同的风险等位基因、效应大小、连锁模式和与烟草相关的暴露。我们假设，在全球人口中罕见或频率较低的种系高外显性变异是 在再生障碍性贫血人群中，富于高危FLC家庭。这个补充项目产生了高覆盖率的全基因组测序；利用可公开获得的非洲人口控制的全基因组测序数据；并利用以家庭为基础的研究设计，确保我们将检测到携带稀有和低频变异的人，这些变异具有更大的影响。