Detecting potential causal relationship between multiple risk factors and Alzheimer’s disease using multivariable Mendelian randomization
Open accessAbstract
BACKGROUND: Alzheimer's disease (AD) is a progressive brain disorder characterized by cognitive skills deterioration that affects many elderly individuals. The identified genetic loci for AD failed to explain the large variability in AD and very few causal factors have been identified so far. RESULTS: =3.564E-05) were associated with increasing AD risk. Genetically predicted FG was suggestively associated with increased AD risk. Furthermore, MR-BMA analysis also confirmed FG and years of schooling as two of the top five causal risk factors for AD. CONCLUSIONS: Our findings might provide us novel insights for treatment and intervention into the causal risk factors for AD or AD-related complex diseases. METHODS: By using extension methods of Mendelian randomization (MR)--multivariable MR (mvMR) and MR based on Bayesian model averaging (MR-BMA), we intend to estimate the potential causal relationship between nine risk factors and AD outcome and try to prioritize the most causal risk factors for AD.
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Altered cholesterol, HDL and LDL metabolism, gene variants of APOA1, APOB, and APOE4, and decreased ApoA1 levels have been implicated in other neurologic disorders.
“Altered cholesterol, HDL and LDL metabolism, gene variants of APOA1, APOB, and APOE4, and decreased ApoA1 levels have been implicated in other neurologic disorders [21–35].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [25]
The Results (mvMR estimates results; page unavailable) associate HDL, LDL, and total cholesterol levels with Alzheimer’s disease risk, supporting the lipid-related part of the claim for that disorder. The paper does not establish altered lipid metabolism across other neurologic disorders, nor does it report associations involving APOA1, APOB, or APOE4 variants or decreased ApoA1 levels. (LLM, conf=0.88)
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- Authors
- Zhang, Q., Xu, F., Wang, L., Zhang, W.-D., Sun, C.-Q., & Deng, H.-W.
- Affiliations
- School of Nursing and Health, Zhengzhou University, High-Tech Development Zone of States, Zhengzhou 450001, P.R. China
- Zhengzhou University (CN)
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, High-Tech Development Zone of States, Zhengzhou 450001, P.R. China
- Tulane University (US)
- Corresponding author
- Deng, Hong-Wen
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2020-11-07
- Volume
- 12
- Issue
- 21
- Pages
- 21747-21757
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC7695397
- OpenAlex
- W3103915724
- Cited by
- 13
- References
- 24
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 3
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (U19AG055373)
- National Institute of Mental Health (R01MH104680)
- National Institute of General Medical Sciences (P20GM109036)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR059781, R01AR069055)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, causal risk factors, multivariable Mendelian randomization, years of schooling, genetic loci, risk factor prioritization
- MeSH terms
- Aged, Alzheimer Disease, Blood Glucose, Female, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Risk Factors, Mendelian Randomization Analysis
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