Asian Cohort for Alzheimer's Disease (ACAD)

项目摘要 阿尔茨海默病(AD)在美国影响着580万人，是我们人类的巨大负担 经济、病人和照顾者。全基因组关联研究(GWAS)已经成功地导致了25 全基因组显着基因座与AD风险相关，以及更多与关键临床协变量的相关性。 这些发现大多是在具有欧洲血统的参与者身上得出的，尽管研究其他 少数民族人口正在腾飞。亚裔美国人对阿尔茨海默病遗传学的了解尤其有限 由于缺少参与者。亚裔美国人占美国人口的6%，样本不足， 应该得到更多的科学投资。 我们提出了亚洲阿尔茨海默病队列(ACAD)，这是第一个大型阿尔茨海默病(AD) 美国和加拿大的亚洲人的遗传学队列。为了优化ACAD的成功，我们组装了一个 由科学家、临床医生和社区合作伙伴组成的团队，在AD研究方面拥有合作历史和专业知识， 人类遗传学和亚裔社区外展。我们建议招募5970名年龄在60岁或以上的参与者 来自美国和加拿大大都会地区的中国、韩国和越南血统的老年人 与服务于亚洲社区的社区合作伙伴、诊所或疗养院合作。我们会收集 唾液中的DNA，并使用经过验证的本地化仪器、数据表格和临床/诊断方案。至 支持这些招聘和数据收集活动，我们将成立协调中心，并制定 治理、社区外联和培训方案，以支持招聘和分析活动；以及 对招聘和外联工作进行流程评估。所有样本都将使用SNP进行基因分型 阵列，并使用来自亚洲的全基因组测序数据的大型亚洲特有参考小组进行推算 国际亚洲同龄人。我们将分析遗传和临床数据，以调查生活方式风险的影响 AD风险的遗传变异因素，评估性别和载脂蛋白E基因类型对AD风险的差异影响，以及 使用遗传和生活方式风险分数预测AD的临床诊断。我们将通过以下方式复制这些发现 与国际亚洲队列和来自其他人群的AD研究的Meta分析合作。 亚裔美国人占美国人口的6%，样本不足，理应得到更多科学研究 对阿尔茨海默病研究的投资。ACAD项目将建立第一个主要的AD遗传学研究 在美国和加拿大的亚洲人。成功完成将导致新的遗传和生活方式筛查标记 为亚裔美国人和对AD的新治疗靶点的见解。ACAD将是第一个 在亚裔美国人中招募和学习AD，将扩展到亚裔印度人、菲律宾人和其他亚洲人 未来的美国人口，满足亚洲人阿尔茨海默病研究的未得到满足的需求 美国人。

Project Summary Alzheimer's disease (AD) affects 5.8 million people in the United States and is an immense burden on our economy, patients and caregivers. Genome-wide association studies (GWAS) have successfully led to 25 genome-wide significant loci associated with AD risk and many more associations with key clinical covariates. Most of these findings are made on participants with European ancestry, although efforts to study other minority populations are taking off. Knowledge about AD genetics among Asian Americans is especially limited due to lack of participants. Comprising 6% of the US populace, Asian Americans are under-sampled and deserve more scientific investment. We propose the Asian Cohort for Alzheimer's Disease (ACAD), the first large Alzheimer's Disease (AD) genetics cohort for Asians in United States (US) and Canada. To optimize ACAD's success, we assembled a team of scientists, clinicians, and community partners with collaborative history and expertise in AD research, human genetics, and Asian community outreach. We propose to recruit 5,970 participants aged 60 years or older and of Chinese, Korean, and Vietnamese ancestry from metropolitan areas across the US and Canada in collaboration with community partners, clinics, or nursing homes that serve Asian communities. We will collect saliva for DNA and use validated, localized instruments, data forms, and clinical/diagnostic protocols. To support these recruitment and data collection activities, we will set up a coordinating center and develop governance, community outreach and training programs to support recruitment and analysis activities, and conduct a process evaluation of the recruitment and outreach efforts. All samples will be genotyped using SNP arrays and imputed using a large Asian-specific reference panel of whole genome sequencing data from international Asian cohorts. We will analyze genetic and clinical data to investigate impact of lifestyle risk factors, genetic variants for AD risk, evaluate differential effects of sex and APOE genotypes on AD risk, and predict clinical diagnosis of AD using genetic and lifestyle risk scores. We will replicate these findings through meta-analysis collaborations with international Asian cohorts and AD studies from other populations. Comprising 6% of the US populace, Asian Americans are under-sampled and deserve more scientific investment in Alzheimer's disease research. The ACAD project will build the first major AD genetics study for Asians in the US and Canada. Successful completion will lead to new genetic and lifestyle screening markers for Asian Americans and insights about novel therapeutic targets for AD. ACAD will be a first network for recruiting and studying AD in Asian Americans that will extend to Asian Indians, Filipino and other Asian American populations in the future, serving the unmet needs of Alzheimer's disease research for Asian Americans.