NG00146 - Singapore Longitudinal study of Vascular Cognitive Impairment and Dementia

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Description

This dataset includes individual level data from Singapore-Longitudinal study of Vascular Cognitive Impairment and Dementia. This includes both genotyping (raw and imputed) on the Infinium Global Screening Array-24 Kit as well as phenotypic data including age, sex, and overall cognitive diagnosis. There were total of 390 subjects that were enrolled in the study and 385 subjects passed QC filtering.

Participants were recruited from memory clinics in 2 study sites in Singapore (National University Hospital and Saint Luke’s Hospital). Four diagnostic categories at baseline were eligible for inclusion in this study:(1) No cognitive impairment (NCI): individuals who had no objective cognitive impairment on neuropsychological tests, or functional loss, (2) Cognitive impairment no dementia (CIND) was diagnosed in patients who were impaired in at least one cognitive domain on a neuropsychological test battery without loss of daily functions. (3) Vascular CIND was defined as a history of ischemic stroke within the past 6–24 months and neuroimaging evidence of cerebral infarction, with objective evidence of neuropsychological deficits. (4) Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria.

Sample Summary per Data Type

Sample Set	Accession	Data Type	Number of Samples
Singapore GWAS	snd10047	Genotyping SNP Array	390

Available Filesets

Name	Accession	Latest Release	Description
Singapore GWAS: Genotype, phenotype and Imputation data	fsa000064	NG00146.v1	Genotype, Phenotype and Imputation data

View the File Manifest for a full list of files released in this dataset.

This dataset contains 390 subjects that were genotyped using the Infinium Global Screening Array-24, resulting in a total of 381,787 genomic SNPs. Of these, 385 subjects passed QC filtering. Additionally, the imputed genotypes are from a 1000G reference panel.

Sample Set	Accession Number	Number of Subjects	Number of Samples
Singapore GWAS	snd10047	390	390

Consent Level	Number of Subjects
HMB-IRB-PUB-NPU-GSO	390

Total number of approved DARs: 1

Investigator:
Belloy, Michael
Institution:
Washington University in St Louis
Project Title:
Elucidating sex-specific risk for Alzheimer's disease through state-of-the-art genetics and multi-omics
Date of Approval:
January 6, 2025
Request status:
Approved
Research use statements:
Show statements
Technical Research Use Statement:
• Objectives: In this project, we seek to holistically investigate the genetic and molecular drivers of sex dimorphism in Alzheimer’s disease across ancestries. • Study design: This study integrates large-scale population genetics with multi-omics and endophenotype analyses. We are integrating all data available from ADGC and ADSP, together with other data from AMP-AD and biobanks such as UKB, FinnGen, and MVP to conduct large-scale multi-ancestry GWAS, rare-variant gene aggregation analyses, QTL studies, PWAS, TWAS, etc. We also particularly focus on X chromosome association studies. The study design also interrogates interactions with ancestry, hormone exposures, and with APOE*4, as well as comparisons to non-stratified GWAS/XWAS of Alzheimer’s disease. Further, we will also employ genetic correlation analyses, mendelian randomization, colocalization, and pleiotropy analyses, to interrogate overlap with other complex traits to better understand the mechanisms underlying sex dimorphism in Alzheimer’s disease. • Analysis plan, including the phenotypic characteristics that will be evaluated in association with genetic variants: Our phenotypes will include Alzheimer’s disease risk, conversion risk, various endophenotypes (including amyloid/tau biomarkers, brain imaging metrics, etc.) as well as molecular traits. As noted above, we will conduct large-scale multi-ancestry GWAS, XWAS, rare-variant gene aggregation analyses, QTL studies, PWAS, TWAS, etc. Specific aims include interrogating these question and analyses on (1) the autosomes, (2) the X chromosome, and (3) leveraging sex stratified QTL studies to drive discovery of risk genes.
Non-Technical Research Use Statement:
Alzheimer’s disease (AD) manifests itself differently across men and women, but the genetic and molecular factors that drive this remain elusive. AD is the most common cause of dementia and till today remains largely untreatable. It is thus crucial to study the genetics of AD in a sex-specific manner, as this will help the field gain important insights into disease pathophysiology, identify novel sex-specific risk factors relevant to personalized genetic medicine, and uncover potential new AD drug targets that may benefit both sexes. This project uses large-scale genomics and multi-omics to elucidate novel sex agnostic and sex-specific AD risk genes. We will interrogate sex dimorphism for AD risk on the autosomes and the sex chromosomes. We similarly interrogate sex dimorphism in the genetic regulation of gene expression and protein levels, which we will integrate with genetic risk for Alzheimer’s disease to further discovery risk genes. Throughout, we will also interrogate how sex-specific risk for AD interactions with hormone exposures, ancestry, and the APOE*4 risk allele.

Total number of samples: 390

Female 213 54.6 %

Male 177 45.4 %

Dementia
Control	83	21.3%
Case	155	39.7%
Other	152	39.0%

NG00146 – Singapore Longitudinal study of Vascular Cognitive Impairment and Dementia

Overview

Description

Sample Summary per Data Type

Available Filesets

Sample information

Related Studies

Cohorts

Consent Levels

Acknowledgement

Acknowledgment statement for any data distributed by NIAGADS:

For investigators using any data from this dataset:

For investigators using Singapore Longitudinal study of Vascular Cognitive Impairment and Dementia (sa000037) data:

Related Publications

Approved Users

Total number of samples: 390