The DOI matches its Crossref record; 78 of the 79 references it cites were found in a registry or an index.
Large Meta-Analysis Establishes the ACE Insertion-Deletion Polymorphism as a Marker of Alzheimer's Disease
Open accessAbstract
Apolipoprotein E epsilon4 (APOE*4) is the only fully established susceptibility allele for Alzheimer's disease. One of the most studied candidates is the insertion (I)/deletion (D) polymorphism (indel) of the gene for angiotensin I-converting enzyme (ACE). This study aimed to clarify its association with Alzheimer's disease. The meta-analysis included 39 samples, comprising 6,037 cases of Alzheimer's disease and 12,099 controls, using mainly primary data. Potential interactions with gender, age, ethnic group, and carrier status of the apolipoprotein E epsilon4 allele were all examined. D homozygotes were at reduced risk of Alzheimer's disease (odds ratio = 0.81, 95% confidence interval: 0.72, 0.90; corrected p = 0.0004); I homozygotes showed no association with Alzheimer's disease, while heterozygotes were at increased risk. Although there were clear differences among the three ethnic groups examined (North Europeans, South Caucasians, and East Asians), in all groups D homozygotes were at reduced risk. These results confirm the association of the angiotensin I-converting enzyme indel with Alzheimer's disease across diverse populations, although this is probably due to linkage disequilibrium with the true risk factor. Further, in North Europeans, both association and Hardy-Weinberg analysis suggested partial heterosis, that is, an increased risk for heterozygotes, due to a hidden interaction with another, as yet unknown, risk factor. This interaction warrants further investigation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“which is a known blood pressure and AD association”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [32]
In the citing paper
“ACE and ADAM10 were previously reported as Alzheimer’s disease candidate genes18–22 but were not replicated in some subsequent studies23–25.”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [22]
In the citing paper
“Candidate gene studies have associated ACE variants with Alzheimer’s disease risk20,22,79, including a strong association in the Wadi Ara, an Israeli Arab community with high risk of Alzheimer’s disease21.”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [22]
Citations
Cites
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722
Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease
(1959) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/22.4.719 · Cited by 14,689
Gentleman R: R: A language for data analysis and graphics
Ihaka, R., & Gentleman, R. (1996) · Journal of Computational and Graphical Statistics · doi:10.1080/10618600.1996.10474713 · Cited by 11,747
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)
Hu, R. J. (2003) · Elsevier eBooks · doi:10.1016/b0-12-226870-9/01070-4 · Cited by 9,168
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961
Rigat, B., Hubert, C., Alhenc-Gelas, F., Cambien, F., Corvol, P., & Soubrier, F. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114844 · Cited by 3,767
Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859
Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499
Research works printed but not linked: 1
- Armitage P. Statistical methods in medical research. Oxford, United Kingdom: Blackwell Scientific Publications, 1983.
Cited by
Sorted by citations
Alzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946
Self-citationSystematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857
GWAS on family history of Alzheimer’s disease
Marioni, R. E., Harris, S. E., Zhang, Q., McRae, A. F., Hagenaars, S. P., Hill, W. D., Davies, G., Ritchie, C. W., Gale, C. R., Starr, J. M., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0150-6 · Cited by 564
Defining the relationship between hypertension, cognitive decline, and dementia: a review
Walker, K. A., Power, M. C., & Gottesman, R. F. (2017) · Current Hypertension Reports · doi:10.1007/s11906-017-0724-3 · Cited by 394
Miners, J. S., Baig, S., Palmer, J. C., Palmer, L. E., Kehoe, P. G., & Love, S. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00132.x · Cited by 393
Self-citation
Metadata
- Authors
- Lehmann, D. J., Cortina-Borja, M., Warden, D. R., Smith, A. D., Sleegers, K., Prince, J. A., van Duijn, C. M., & Kehoe, P. G.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Lehmann, Donald J.
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-08-15
- Volume
- 162
- Issue
- 4
- Pages
- 305-317
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- OpenAlex
- W2044936845
- Cited by
- 199
- References
- 79
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 8 · 2022: 3 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 7 · 2014: 15 · 2013: 9 · 2012: 9
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- American Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- 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, angiotensin-converting enzyme, ACE I/D polymorphism, APOE ε4, genetic susceptibility, genetic association, linkage disequilibrium, heterosis, ethnic differences, Hardy-Weinberg equilibrium, risk factors
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Ethnicity, Female, Humans, Hybrid Vigor, Peptidyl-Dipeptidase A, Male, Middle Aged, Polymorphism, Genetic, Confidence Intervals, Apolipoprotein E4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
