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Replication of CLU, CR1, and PICALM Associations With Alzheimer Disease
Open accessAbstract
OBJECTIVE: To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease. DESIGN: Follow-up case-control association study. SETTING: The Mayo Clinics at Jacksonville, Florida, and Rochester, Minnesota. PARTICIPANTS: Community-based patients of European descent with late-onset Alzheimer disease (LOAD) and controls without dementia who were seen at the Mayo clinics, and autopsy-confirmed cases and controls whose pathology was evaluated at the Mayo Clinic in Jacksonville. Additional samples were obtained from the National Cell Repository for Alzheimer Disease (NCRAD). A total of 1829 LOAD cases and 2576 controls were analyzed. INTERVENTIONS: The most significant single-nucleotide polymorphisms in CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179) were tested for allelic association with LOAD. Main Outcome Measure Clinical or pathology-confirmed diagnosis of LOAD. RESULTS: Odds ratios for CLU, CR1, and PICALM were 0.82, 1.15, and 0.80, respectively, comparable in direction and magnitude with those originally reported. P values were 8.6 x 10(-5), .014, and 1.3 x 10(-5), respectively; they remain significant even after Bonferroni correction for the 3 single-nucleotide polymorphisms tested. CONCLUSION: These results show near-perfect replication and provide the first additional evidence that CLU, CR1, and PICALM are associated with the risk of LOAD.
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“The association of PICALM polymorphisms with late-onset AD has been reported by the majority of GWAS studies (94, 119, 236, 265, 298, 344, 528).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [94]
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“Some additional highly replicated risk genes include CR1 , BIN1 , and TREM2 (94, 119, 219, 300, 344, 543).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [94]
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“Several GWAS studies have identified CLU as a significant genetic risk factor for sporadic AD (94, 119, 236, 343).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [94]
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Metadata
- Authors
- Carrasquillo, M. M., Belbin, O., Hunter, T. A., Ma, L., Bisceglio, G. D., Zou, F., Crook, J. E., Pankratz, V. S., Dickson, D. W., Graff-Radford, N. R., Petersen, R. C., Morgan, K., & Younkin, S. G.
- Affiliations
- Mayo Clinic in Florida (US)
- Mayo Clinic (US)
- University of Nottingham (GB)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2010-08-01
- Volume
- 67
- Issue
- 8
- Pages
- 961-4
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC2919638
- OpenAlex
- W2065929647
- Cited by
- 208
- References
- 24
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 1 · 2022: 7 · 2021: 6 · 2020: 11 · 2019: 5 · 2018: 15 · 2017: 8 · 2016: 17 · 2015: 13 · 2014: 23 · 2013: 23 · 2012: 29
- FWCI
- 20.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (U01 AG 06576, P50‐AG16574, AG03949, R01AG018023, U01AG006786, P01AG003949, AG 25711, R01-AG18023, AG 17216, U24 AG21886, P50AG025711, P01AG017216, U24AG021886, P50AG016574)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, late-onset Alzheimer's disease, CLU gene, genetic association, single nucleotide polymorphisms, genetic risk factors, replication study
- MeSH terms
- Alzheimer Disease, Follow-Up Studies, Gene Frequency, Genotype, Humans, Residence Characteristics, Odds Ratio, Case-Control Studies, Receptors, Complement 3b, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Monomeric Clathrin Assembly Proteins, White People, Clusterin, Genome-Wide Association Study
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