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Title | Identification of novel genes for age-at-onset of Alzheimer's disease by combining quantitative and survival trait analyses. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Li Y-J, Nuytemans K, La JOk, Jiang R, Slifer SH, Sun S, Naj A, Gao XRaymond, Martin ER |
Journal | Alzheimers Dement |
Volume | 19 |
Issue | 7 |
Pagination | 3148-3157 |
Date Published | 07/2023 |
ISSN | 1552-5279 |
Keywords | Age of Onset, Alzheimer Disease, DNA-Binding Proteins, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Phenotype, Polymorphism, Single Nucleotide |
Abstract | INTRODUCTION: Our understanding of the genetic predisposition for age-at-onset (AAO) of Alzheimer's disease (AD) is limited. Here, we sought to identify genes modifying AAO and examined whether any have sex-specific effects. METHODS: Genome-wide association analysis were performed on imputed genetic data of 9219 AD cases and 10,345 controls from 20 cohorts of the Alzheimer's Disease Genetics Consortium. AAO was modeled from cases directly and as a survival outcome. RESULTS: We identified 11 genome-wide significant loci (P < 5 × 10 ), including six known AD-risk genes and five novel loci, UMAD1, LUZP2, ARFGEF2, DSCAM, and 4q25, affecting AAO of AD. Additionally, 39 suggestive loci showed strong association. Twelve loci showed sex-specific effects on AAO including CD300LG and MLX/TUBG2 for females and MIR4445 for males. DISCUSSION: Genes that influence AAO of AD are excellent therapeutic targets for delaying onset of AD. Several loci identified include genes with promising functional implications for AD. |
DOI | 10.1002/alz.12927 |
Alternate Journal | Alzheimers Dement |
PubMed ID | 36738287 |
Grant List | RF1AG060472 / / National Institutes of Health, National Institute on Aging / R01AG062634 / / National Institutes of Health, National Institute on Aging / U01AG032984 (Alzheimer's Disease Genetics Consortium) / / National Institutes of Health, National Institute on Aging / |