Asian Cohort for Alzheimer's Disease (ACAD)

总体摘要 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。为了解决招聘障碍，我们召集了 一个由科学家、临床医生和社区合作伙伴组成的团队，他们在AD研究方面拥有合作的历史和专业知识， 人类遗传学和亚裔社区外展。我们建议招募5,081名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卫生服务提供者或长期护理机构合作。我们 将收集DNA和血浆生物标记物，并使用经过验证、翻译的数据收集表格和 临床/诊断方案。为了支持这些招聘和数据收集活动，我们将组成六个核心 提供现场管理、外展、临床专业知识、数据管理、生物样本管理、 以及培训和质量保证，以支持征聘和分析活动。所有样品都将是 使用SNP阵列进行基因分型，并使用大型亚洲特有的全基因组参考小组进行推算 对来自国际亚洲队列的数据进行测序。我们提出了两个研究项目，将分析基因， 生物标记物和临床数据调查生活方式风险因素的影响，AD风险的基因变异，评估 性别和载脂蛋白E基因对AD风险的不同影响，并利用基因预测AD的临床诊断 和生活方式风险得分。我们将通过元分析合作复制这些发现 来自其他人群的国际亚洲队列和AD研究。

Overall Abstract 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 address recruitment barriers, 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 5,081 participants aged 60 years or older and of Chinese, Korean, and Vietnamese ancestry from metropolitan areas across US and Canada in collaboration with community health providers or long-term care facilities that serve Asian communities. We will collect DNA and plasma biomarkers and use validated, translated data collection forms and clinical/diagnostic protocols. To support these recruitment and data collection activities, we will form six Cores that provide administrative oversite, outreach, clinical expertise, data management, biosample management, and training and quality assurance to support recruitment and analysis activities. 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 propose two Research Projects that will analyze genetic, biomarker 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.