Imaging genomics discovery of a new risk variant for Alzheimer's disease in the postsynaptic SHARPIN gene.
Aged
Aged, 80 and over
Alzheimer Disease
/ diagnostic imaging
Cognitive Dysfunction
/ diagnostic imaging
Cross-Sectional Studies
Entorhinal Cortex
/ diagnostic imaging
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Imaging Genomics
Limbic System
/ diagnostic imaging
Longitudinal Studies
Magnetic Resonance Imaging
Male
Neuroimaging
Post-Synaptic Density
/ metabolism
Ubiquitins
/ genetics
White Matter
/ diagnostic imaging
Alzheimer's disease
brain atrophy
independent component analysis
synaptic adhesion
tensor-based morphometry
whole-genome sequencing
Journal
Human brain mapping
ISSN: 1097-0193
Titre abrégé: Hum Brain Mapp
Pays: United States
ID NLM: 9419065
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
19
02
2020
revised:
29
04
2020
accepted:
14
05
2020
pubmed:
20
6
2020
medline:
15
12
2021
entrez:
20
6
2020
Statut:
ppublish
Résumé
Molecular mechanisms underlying Alzheimer's disease (AD) are difficult to investigate, partly because diagnosis lags behind the insidious pathological processes. Therefore, identifying AD neuroimaging markers and their genetic modifiers may help study early mechanisms of neurodegeneration. We aimed to identify brain regions of the highest vulnerability to AD using a data-driven search in the AD Neuroimaging Initiative (ADNI, n = 1,100 subjects), and further explored genetic variants affecting this critical brain trait using both ADNI and the younger UK Biobank cohort (n = 8,428 subjects). Tensor-Based Morphometry (TBM) and Independent Component Analysis (ICA) identified the limbic system and its interconnecting white-matter as the most AD-vulnerable brain feature. Whole-genome analysis revealed a common variant in SHARPIN that was associated with this imaging feature (rs34173062, p = 2.1 × 10
Identifiants
pubmed: 32558014
doi: 10.1002/hbm.25083
pmc: PMC7416020
doi:
Substances chimiques
SHARPIN protein, human
0
Ubiquitins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3737-3748Subventions
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG059871
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG058854
Pays : United States
Organisme : Radboud Universitair Medisch Centrum
ID : R0003664
Organisme : Biogen
ID : PO 969323
Informations de copyright
© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.
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