| Title: |
Genetic complexities of cerebral small vessel disease, blood pressure, and dementia |
| Authors: |
Sargurupremraj, M; Soumaré, A; Bis, JC; Surakka, I; Jürgenson, T; Joly, P; Knol, MJ; Wang, R; Yang, Q; Satizabal, CL; Gudjonsson, A; Mishra, A; Bouteloup, V; Phuah, C-L; Van Duijn, CM; Cruchaga, C; Dufouil, C; Chêne, G; Lopez, OL; Psaty, BM; Tzourio, C; Amouyel, P; Adams, HH; Jacqmin-Gadda, H; Ikram, MA; Gudnason, V; Milani, L; Winsvold, BS; Hveem, K; Matthews, PM; Longstreth, WT; Seshadri, S; Launer, LJ; Debette, S |
| Publisher Information: |
JAMA Network |
| Publication Year: |
2024 |
| Collection: |
Imperial College London: Spiral |
| Subject Geographic: |
United States |
| Description: |
IMPORTANCE: Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain. OBJECTIVE: To investigate the causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and dementia risk, while accounting for potential epidemiologic biases. DESIGN, SETTING, AND PARTICIPANTS: This study first examined the association of genetically determined WMH burden, stroke, and BP levels with Alzheimer disease (AD) in a 2-sample mendelian randomization (2SMR) framework. Second, using population-based studies (1979-2018) with prospective dementia surveillance, the genetic association of WMH, stroke, and BP with incident all-cause dementia was examined. Data analysis was performed from July 26, 2020, through July 24, 2022. EXPOSURES: Genetically determined WMH burden and BP levels, as well as genetic liability to stroke derived from genome-wide association studies (GWASs) in European ancestry populations. MAIN OUTCOMES AND MEASURES: The association of genetic instruments for WMH, stroke, and BP with dementia was studied using GWASs of AD (defined clinically and additionally meta-analyzed including both clinically diagnosed AD and AD defined based on parental history [AD-meta]) for 2SMR and incident all-cause dementia for longitudinal analyses. RESULTS: In 2SMR (summary statistics-based) analyses using AD GWASs with up to 75 024 AD cases (mean [SD] age at AD onset, 75.5 [4.4] years; 56.9% women), larger WMH burden showed evidence for a causal association with increased risk of AD (odds ratio [OR], 1.43; 95% CI, 1.10-1.86; P = .007, per unit increase in WMH risk alleles) and AD-meta (OR, 1.19; 95% CI, 1.06-1.34; P = .008), after accounting for pulse pressure for the former. Blood pressure traits showed evidence for a protective association with AD, with evidence for confounding by shared genetic instruments. In the longitudinal (individual-level data) analyses involving 10 699 incident all-cause ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
JAMA Network Open; http://hdl.handle.net/10044/1/112235 |
| DOI: |
10.1001/jamanetworkopen.2024.12824 |
| Availability: |
http://hdl.handle.net/10044/1/112235; https://doi.org/10.1001/jamanetworkopen.2024.12824 |
| Rights: |
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2024 Sargurupremraj M et al. JAMA Network Open. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.4952DAD2 |
| Database: |
BASE |