Effects of ApoE4 and ApoE2 genotypes on subcortical magnetic susceptibility and microstructure in 27,535 participants from the UK Biobank
Talia M Nir, Alyssa H Zhu, Iyad Ba Gari, Daniel Dixon, Tasfiya Islam, Julio E Villalon-Reina, Sarah E Medland, Paul M Thompson et al.. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2022
Topic: Genetics and APOE
Disrupted iron homeostasis is associated with several neurodegenerative diseases, including Alzheimer's disease (AD), and may be partially modulated by genetic risk factors. Here we evaluated whether subcortical iron deposition is associated with ApoE genotype, which substantially affects risk for late-onset AD. We evaluated differences in subcortical quantitative susceptibility mapping (QSM), a type of MRI sensitive to cerebral iron deposition, between either ApoE4 (E3E4+E4E4) or ApoE2 (E2E3+E2E2) carriers and E3 homozygotes (E3E3) in 27,535 participants from the UK Biobank (age: 45-82 years). We found that ApoE4 carriers had higher hippocampal (d=0.036; p=0.012) and amygdalar (d=0.035; p=0.013) magnetic susceptibility, particularly individuals aged 65 years or older, while those carrying ApoE2 (which protects against AD) had higher QSM only in the hippocampus (d=0.05; p=0.006), particularly those under age 65. Secondary diffusion MRI microstructural associations in these regions revealed greater diffusivity and less diffusion restriction in E4 carriers, however no differences were detected in E2 carriers. Disease risk conferred by ApoE4 may be linked with higher subcortical iron burden in conjunction with inflammation or neuronal loss in aging individuals, while ApoE2 associations may not necessarily reflect unhealthy iron deposits earlier in life.
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APA 7th
Nir, T. M., Zhu, A. H., Gari, I. B., Dixon, D., Islam, T., Villalon-Reina, J. E., et al. (2022). Effects of ApoE4 and ApoE2 genotypes on subcortical magnetic susceptibility and microstructure in 27,535 participants from the UK Biobank. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.
Vancouver
Nir TM, Zhu AH, Gari IB, Dixon D, Islam T, Villalon-Reina JE, et al. Effects of ApoE4 and ApoE2 genotypes on subcortical magnetic susceptibility and microstructure in 27,535 participants from the UK Biobank. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 2022. PMID: 34890142.
BibTeX
@article{nir2022-34890142,
author = {Nir, Talia M and Zhu, Alyssa H and Gari, Iyad Ba and Dixon, Daniel and Islam, Tasfiya and Villalon-Reina, Julio E and Medland, Sarah E and Thompson, Paul M and others},
title = {{Effects of ApoE4 and ApoE2 genotypes on subcortical magnetic susceptibility and microstructure in 27,535 participants from the UK Biobank}},
journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing},
year = {2022},
pmid = {34890142}
}
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Key findings
- Disrupted iron homeostasis is associated with several neurodegenerative diseases, including Alzheimer's disease (AD), and may be partially modulated by genetic risk factors.
- Here we evaluated whether subcortical iron deposition is associated with ApoE genotype, which substantially affects risk for late-onset AD.
- We found that ApoE4 carriers had higher hippocampal (d=0.036; p=0.012) and amygdalar (d=0.035; p=0.013) magnetic susceptibility, particularly individuals aged 65 years or older, while those carrying ApoE2 (which protects against AD) had higher QSM only in the hippocampus (d=0.05; p=0.006), particularly those under age 65.
- Secondary diffusion MRI microstructural associations in these regions revealed greater diffusivity and less diffusion restriction in E4 carriers, however no differences were detected in E2 carriers.
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Study details
- Participants27,535
- Evidence strengthLow
How this study scored 54/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multicenter collaboration and free to read, so those were left out: it earned 30 of the 56 points we could judge it on, which is 54 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 4 / 4 | 27,535 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34890142) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 30 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 30 of the 56 points we could judge it on is 54 out of 100. |
| Total | 54 / 100 | — |
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