Multi-Ancestry Mapping of Pancreatic Cancer Susceptibility Loci

这项应用的目的是提高我们对胰腺癌遗传基础的理解。 胰腺癌目前是美国癌症死亡的第三大原因，据预测 2019年，美国将新增56,770例胰腺癌确诊病例。在过去十年中， 胰腺癌的发病率一直在稳步上升。尽管胰腺癌的发病率 与美国白人人口相比，非裔美国人的比例更高。 迄今为止，在非裔美国人中进行了大规模的胰腺癌遗传学研究。此外，相对的 胰腺导管腺癌(PDAC)的罕见和迅速致命的病程已导致 所有先前的全基因组关联研究的样本大小有限，而不考虑祖先群体。AS 由于统计能力有限，许多常见的PDAC基因座尚未确定。大规模、多样化 需要对PDAC进行合作研究，以显著增加我们对PDAC遗传基础的理解 这种致命的疾病。我们的建议就是专门针对这一需求而设计的。首先，我们将进行第一次 通过全基因组对胰腺癌风险的遗传学研究特别集中在非裔美国人 测序。作为这项研究的一部分，我们汇集了非裔美国人胰腺癌患者和 来自我们两个成功的大型胰腺癌财团--胰腺癌的控制 队列联盟和胰腺癌病例控制联盟(PanC4)。其次，我们还扩大了 我们通过将以前的GWA规模扩大一倍来检测所有种族的胰腺癌关联的能力 研究并进行首个胰腺癌风险的多种族遗传研究。我们将进行这两项工作 世系分层和世系信息分析，包括单一变异和基于基因的检测 胰腺癌患者和对照的协会。此外，我们还将进行基因x环境 与吸烟、体重指数、糖尿病和饮酒等已知危险因素的交互作用分析。的具体目标 该项目是为了：目标1：确定非裔美国人人群中胰腺癌的易感基因， 目标2：通过多种族GWAS分析确定新的胰腺癌基因座；目标3：精细定位 与胰腺癌风险相关的区域。综上所述，该应用程序试图识别新的胰腺 癌症基因，首次在非洲血统的个人中进行胰腺癌的基因分析，以及 利用跨种群遗传多样性精细绘制已知的胰腺癌易感基因座图。 好了！

The goal of this application is to improve our understanding of the genetic basis of pancreatic cancer. Pancreatic cancer is currently the 3rd leading cause of cancer death in the United States and it is projected there will be 56,770 new pancreatic cancer diagnosed in the United States in 2019. Over the past decade the incidence of pancreatic cancer has been steadily increasing. Despite the fact that pancreatic cancer incidence rates are higher among African Americans compared to the US White population there have been no large- scale genetic studies of pancreatic cancer in African Americans conducted to date. Furthermore, the relative rarity of pancreatic ductal adenocarcinoma cancer (PDAC) and the rapidly fatal disease course has resulted in limited samples sizes for all prior genome-wide association studies regardless of ancestral population. As such many common PDAC loci have yet to be identified due to limited statistical power. Large-scale, diverse collaborative studies of PDAC, are needed to dramatically increase our understanding of the inherited basis of this deadly disease. Our proposal is designed to specifically address this need. First, we will conduct the first genetic study of pancreatic cancer risk specifically focused on African Americans through whole genome sequencing. As part of this study we are bringing together African American pancreatic cancer patients and controls from our two, large established, successful pancreatic cancer consortiums, the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case Control Consortium (PanC4). Secondly, we also expand our power to detect pancreatic cancer association across all ethnic groups by doubling the size of prior GWAS studies and conducting the first multi-ethnic genetic study of pancreatic cancer risk. We will conduct both ancestry stratified and ancestry-informed analysis including both single variant and gene-based tests of association of pancreatic cancer patients and controls. In addition, we will conduct gene x environment interaction analysis with known risk factors of smoking, BMI, diabetes, and alcohol intake. The specific aims of the project are to: Aim 1: To identify pancreatic cancer susceptibility loci in the African American population, Aim 2: To identify novel pancreatic cancer loci through multi-ethnic GWAS analyses; Aim 3: To fine-map regions associated with pancreatic cancer risk. In summary, this application seeks to identify novel pancreatic cancer loci, conduct the first genetic analysis of pancreatic cancer in individuals of African Ancestry, and leverage cross population genetic diversity to fine-map known pancreatic cancer susceptibility loci. !