Asian Cohort for Alzheimer's Disease (ACAD)

总体摘要 阿尔茨海默病（AD）影响美国580万人，是我们国家的巨大负担。 经济、患者和护理人员。全基因组关联研究（GWAS）已成功地导致25个 与AD风险相关的全基因组显著位点以及与关键临床协变量的更多相关性。 大多数这些发现都是对欧洲血统的参与者进行的，尽管研究其他人的努力， 少数民族人口正在增加。亚裔美国人对AD遗传学的了解尤其有限 由于缺乏参与者。亚裔美国人占美国人口的6%，但他们的样本不足， 值得更多的科学投资。 我们提出了阿尔茨海默病亚洲队列（ACAD），第一个大型阿尔茨海默病（AD） 美国（US）和加拿大的亚洲人遗传学队列。为了解决招聘障碍，我们聚集了 一个由科学家、临床医生和社区合作伙伴组成的团队，在AD研究方面具有合作历史和专业知识， 人类遗传学和亚洲社区外展。我们建议招募5，081名60岁或以上的参加者， 来自美国和加拿大大都市地区的中国、韩国和越南血统的老年人， 与社区卫生服务提供者或为亚裔社区服务的长期护理机构合作。我们 将收集DNA和血浆生物标志物，并使用经验证的翻译数据收集表， 临床/诊断协议。为了支持这些招募和数据收集活动，我们将成立六个核心小组， 提供行政管理、外联、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。所有样品将 使用SNP阵列进行基因分型，并使用全基因组的大型亚洲特异性参考组进行插补 来自国际亚洲队列的测序数据。我们提出了两个研究项目，将分析遗传， 生物标志物和临床数据，以研究生活方式风险因素、遗传变异对AD风险的影响， 性别和APOE基因型对AD风险的不同影响，并使用遗传学方法预测AD的临床诊断 和生活方式风险评分。我们将通过荟萃分析合作复制这些发现， 国际亚洲队列和其他人群的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.