Document detail
ID
oai:www.zora.uzh.ch:234760
Topic
Clinic for Psychiatry, Psychothera... Department of Child and Adolescent... Neuroscience Center Zurich Center for Integrative Human Physi... 610 Medicine & health General MedicineAuthor
Luo, Jiao Thomassen, Jesper Qvist Bellenguez, Céline Grenier-Boley, Benjamin de Rojas, Itziar Castillo, Atahualpa Parveen, Kayenat Küçükali, Fahri Nicolas, Aude Peters, Oliver Schneider, Anja Dichgans, Martin Rujescu, Dan Scherbaum, Norbert Jürgen, Deckert Riedel-Heller, Steffi Hausner, Lucrezia Porcel, Laura Molina Düzel, Emrah Grimmer, Timo Wiltfang, Jens Heilmann-Heimbach, Stefanie Moebus, Susanne Tegos, Thomas Scarmeas, Nikolaos Clarimon, Jordi Moreno, Fermin Pérez-Tur, Jordi Bullido, María J et al Grünblatt, Edna https://orcid.org/0000-0001-8505-7265 Popp, Julius https://orcid.org/0000-0002-0068-0312Langue
engEditor
American Medical Association (AMA)
Category
Subjects = 04 Faculty of Medicine
Year
2023
listing date
10/12/2023
Keywords
alzheimer control hdl dementia systolic odds cholesterol factors pressure blood genetic increase modifiable [95% ci participants risk genetically determined adAbstract
Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course.
However, robust evidence for most of these risk factors is lacking.
Effective interventions should target risk factors in the causal pathway to dementia.
Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.
Design, setting, and participants: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization.
Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia.
Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021.
Main analyses were conducted using the EADB clinically diagnosed end point data.
All analyses were performed between April 12 and October 27, 2022.
Exposures: Genetically determined modifiable risk factors.
Main outcomes and measures: Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors.
Results: The EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD.
The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants.
Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female.
Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]).
Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]).
In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]).
Conclusions and relevance: This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD.
These findings may inspire new drug targeting and improved prevention implementation.
Luo, Jiao,Thomassen, Jesper Qvist,Bellenguez, Céline,Grenier-Boley, Benjamin,de Rojas, Itziar,Castillo, Atahualpa,Parveen, Kayenat,Küçükali, Fahri,Nicolas, Aude,Peters, Oliver,Schneider, Anja,Dichgans, Martin,Rujescu, Dan,Scherbaum, Norbert,Jürgen, Deckert,Riedel-Heller, Steffi,Hausner, Lucrezia,Porcel, Laura Molina,Düzel, Emrah,Grimmer, Timo,Wiltfang, Jens,Heilmann-Heimbach, Stefanie,Moebus, Susanne,Tegos, Thomas,Scarmeas, Nikolaos,Clarimon, Jordi,Moreno, Fermin,Pérez-Tur, Jordi,Bullido, María J,et al,Grünblatt, Edna, https://orcid.org/0000-0001-8505-7265,Popp, Julius, https://orcid.org/0000-0002-0068-0312, 2023, Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease, American Medical Association (AMA)
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