Association of Alzheimer's disease GWAS loci with MRI markers of brain aging
Chauhan G, Adams HHH, Bis JC, Weinstein G, Yu L, Töglhofer AM, Smith AV, van der Lee SJ et al.. Neurobiology of aging, 2015-01-06
Topic: Amyloid, tau and blood-test diagnosis
Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.
Key findings
- In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058).
- A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029).
- However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested).
- These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.
Why it matters
In this meta-analysis, a genetic risk score for Alzheimer disease was associated with smaller hippocampal volume, though only the association including APOE remained significant after correcting for multiple tests. It suggests risk genes may affect brain structure in people without dementia, but shows no treatment or prevention.
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Study details
- Study designmeta-analysis
- Participants8,175
- Evidence strengthHigh
Limitations
These are statistical associations in population samples rather than a clinical Alzheimer's cohort, and the effect sizes for genes other than APOE and CD33 are not described in the abstract available here.
How this study scored 69/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 8,175 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 4 / 7 | Cited 98 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Stéphanie Debette: h-index 96 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 41 institution(s) in 11 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25670335) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
- DOI: 10.1016/j.neurobiolaging.2014.12.028
- PubMed: 25670335
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Chauhan, G., Adams, H. H. H., Bis, J. C., Weinstein, G., Yu, L., Töglhofer, A. M., et al. (2015). Association of Alzheimer's disease GWAS loci with MRI markers of brain aging. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2014.12.028
Vancouver
Chauhan G, Adams HHH, Bis JC, Weinstein G, Yu L, Töglhofer AM, et al. Association of Alzheimer's disease GWAS loci with MRI markers of brain aging. Neurobiology of aging. 2015. doi:10.1016/j.neurobiolaging.2014.12.028. PMID: 25670335.
BibTeX
@article{chauhan2015-25670335,
author = {Chauhan, G. and Adams, H. H. H. and Bis, J. C. and Weinstein, G. and Yu, L. and Töglhofer, A. M. and Smith, A. V. and van der Lee, S. J. and others},
title = {{Association of Alzheimer's disease GWAS loci with MRI markers of brain aging}},
journal = {Neurobiology of aging},
year = {2015},
doi = {10.1016/j.neurobiolaging.2014.12.028},
pmid = {25670335},
url = {https://doi.org/10.1016/j.neurobiolaging.2014.12.028}
}
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