Faculty, Staff and Student Publications
Publication Date
12-1-2024
Journal
Alzheimer's & Dementia
Abstract
INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.
METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.
RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10
DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.
HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. We identified genetic variants at apolipoprotein E (APOE), BIN1, PSEN1, and LINC00320 associated with AD. We observed rare non-coding variants in the promoter of TOMM40 distinct of APOE.
Keywords
Humans, Alzheimer Disease, Whole Genome Sequencing, Apolipoproteins E, Male, Female, Tumor Suppressor Proteins, Presenilin-1, Aged, Genetic Predisposition to Disease, Mitochondrial Precursor Protein Import Complex Proteins, Genetic Variation, Adaptor Proteins, Signal Transducing, Membrane Transport Proteins, Nuclear Proteins, Haplotypes, Alzheimer's disease, genetics, rare genetic variants, whole genome sequencing
DOI
10.1002/alz.14283
PMID
39428839
PMCID
PMC11667527
PubMedCentral® Posted Date
10-20-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Cognition and Perception Commons, Medical Genetics Commons, Neurology Commons, Neurosciences Commons, Public Health Commons