Polymorphisms in LMNA and near a SERPINA gene cluster are associated with cognitive function in older people
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A recent genome-wide association (GWA) study of late-onset Alzheimer's disease (LOAD) identified 15 novel single nucleotide polymorphisms (SNPs) independent of ApoE. We hypothesised that variants associated with LOAD are also associated with poor cognitive function in elderly populations. We measured additive associations between the five most strongly associated LOAD SNPs and grouped Mini Mental State Examination (MMSE) scores. Variants were genotyped in respondents (mean age 79 years) from the Oxford Healthy Ageing project (OHAP) and other sites of the MRC Cognitive Function and Ageing Study (MRC-CFAS). In adjusted ordinal logistic models, two variants were associated with poorer cognitive function: rs11622883 (OR=1.14, 95% CI: 1.01-1.28, p=0.040) and rs505058 (OR=1.29, 95% CI: 1.02-1.64, p=0.036). These SNPs are close to a SERPINA gene cluster and within LMNA, respectively. The mechanisms underlying the associations with cognitive impairment and LOAD require further elucidation, but both genes are interesting candidates for involvement in age-related cognitive impairment.
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Variations in Serpina3m and n have been associated with cognitive function in human aging and Alzheimer's disease vulnerability.
“Interestingly the top 2 genes upregulated by aging in all regions were the reactive astrocyte genes Serpina3m and n, variations in which have been associated with cognitive function in human aging and Alzheimer’s disease vulnerability (Cluett et al., 2010).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Cluett et al., 2010
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The aging astrocyte transcriptome from multiple regions of the mouse brain.
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- Authors
- Cluett, C., Brayne, C., Clarke, R., Evans, G., Matthews, F., Rubinsztein, D. C., Huppert, F., Llewellyn, D. J., Rice, N., Henley, W., Frayling, T. M., Murray, A., & Melzer, D.
- Affiliations
- Royal Devon and Exeter Hospital (GB)
- University of Cambridge (GB)
- University of Oxford (GB)
- MRC Biostatistics Unit (GB)
- Addenbrooke's Hospital (GB)
- Corresponding author
- Melzer, David
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 31
- Issue
- 9
- Pages
- 1563-1568
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2975102
- OpenAlex
- W2115007439
- Cited by
- 12
- References
- 32
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2018: 2 · 2015: 2 · 2013: 1
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (064354)
- National Institute for Health and Care Research
- Medical Research Council
- National Institute on Aging (R01AG24233, R01AG024233)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- lamin A/C, single nucleotide polymorphisms, late-onset Alzheimer's disease, cognitive function, age-related cognitive impairment, older adults, Mini-Mental State Examination, genetic susceptibility
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Cognition Disorders, Female, Multigene Family, United Kingdom, Humans, Polymorphism, Genetic, Risk Factors, Linkage Disequilibrium, Serpins, Comorbidity, Causality, Incidence, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Lamin Type A
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