Diagnosis of Alzheimer’s disease using GWAS, blood transcriptome and blood biomarkers

- Objectives of the proposed research: The primary objective of this research is to validate the findings from our analysis of whole genome sequencing data in Koreans by replicating them using the ADSP dataset, particularly focusing on individuals from diverse ethnic backgrounds. Our previous analyses aimed to identify associations between genetic variants and Alzheimer's disease (AD), with a specific focus on early-onset Alzheimer's disease (EOAD), by analyzing whole genome sequencing data and performing both variant-level and gene-level statistical analyses. By leveraging the requested ADSP data, we aim to confirm these associations and improve the accuracy of our findings.

- Study design: This research follows a cross-sectional design. We will utilize data from EOAD patients and control groups recruited at Seoul National University Bundang Hospital to perform rare-variant association analyses, focusing on their association with AD diagnosis. Based on the results of our analysis, we will conduct replication studies using the ADSP dataset, which includes participants of various ethnicities and comprehensive phenotypes. This study is part of our larger project, "Diagnosis of Alzheimer’s disease using GWAS, blood transcriptome and blood biomarkers", which aims to integrate genetic findings with transcriptome data and other biomarkers to improve the diagnostic accuracy of AD.

- Analysis plan, including the phenotypic characteristics that will be evaluated in association with genetic variants: The analysis using the ADSP dataset will focus on replicating previous findings related to EOAD diagnosis using whole genome sequencing data in Koreans. We will evaluate the association between variants identified in our analysis and various phenotypic characteristics in the ADSP dataset, such as cognitive function and biomarkers, including β-amyloid, phosphorylated tau, and other Alzheimer-related markers measured by different tools.

- Collaborations: There are no planned collaborations with researchers at other institutions for this study.

This study aims to better understand the genetic factors associated with early-onset Alzheimer's disease (EOAD), particularly among diverse populations. By analyzing whole genome sequencing data from Koreans, we have identified certain genetic variants linked to EOAD. We will now replicate these findings using data from the Alzheimer's Disease Sequencing Project (ADSP), which includes individuals of various ethnicities. Through this research, we hope to improve the accuracy of Alzheimer's disease diagnosis by identifying genetic risk factors that contribute to the development of the disease, ultimately aiding in early detection and treatment.