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Association of APOE With Primary Open-Angle Glaucoma Suggests a Protective Effect for APOE ε4
Margeta MA, Letcher SM, Igo RP, Cooke Bailey JN, Pasquale LR, Haines JL, Butovsky O, Wiggs JL et al.. Investigative ophthalmology & visual science, 2020-07-01
Topic: Brain proteins, microglia and lab models
Purpose Prior studies have demonstrated that microglial activation is involved in the pathogenesis of primary open-angle glaucoma (POAG). Here we sought to identify genetic associations between POAG and variants in APOE and TREM2, genes associated with Alzheimer disease (AD) that critically regulate microglial neurodegeneration-associated molecular signature. Methods APOE genotypes were called using imputed data from the NEIGHBOR consortium (2120 POAG cases, 2262 controls) and a second cohort from the Massachusetts Eye and Ear Infirmary (MEEI; 486 cases, 344 controls). TREM2 coding variants were genotyped by means of the Illumina HumanExome BeadArray. The data set was analyzed for association with POAG overall, as well as the high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) subgroups, using logistic regression adjusting for age and sex. Results In the combined NEIGHBOR-MEEI data set, significant association was observed for APOE ε4 in POAG overall (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.74-0.94; P = 0.0022) and in both the HTG subgroup (OR, 0.81; 95% CI, 0.70-0.94; P = 0.0052) and NTG subgroup (OR, 0.71; 95% CI, 0.58-0.87; P = 0.0014). A rare TREM2 variant (A105V) was found only in HTG cases (3 of 2863 cases) and in none of the controls (P = 0.03). Three TREM2 rare variants associated with AD were not significantly associated with POAG (P > 0.05). Conclusions We have found that the APOE ε4 allele is associated with a reduced risk of POAG. Interestingly, the same allele is adversely associated with AD, suggesting a mechanistic difference between neurodegenerative diseases of the eye and the brain. TREM2 variants associated with AD did not significantly contribute to POAG risk.
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APA 7th
Margeta, M. A., Letcher, S. M., Igo, R. P., Cooke Bailey, J. N., Pasquale, L. R., Haines, J. L., et al. (2020). Association of APOE With Primary Open-Angle Glaucoma Suggests a Protective Effect for APOE ε4. Investigative ophthalmology & visual science. https://doi.org/10.1167/iovs.61.8.3
Vancouver
Margeta MA, Letcher SM, Igo RP, Cooke Bailey JN, Pasquale LR, Haines JL, et al. Association of APOE With Primary Open-Angle Glaucoma Suggests a Protective Effect for APOE ε4. Investigative ophthalmology & visual science. 2020. doi:10.1167/iovs.61.8.3. PMID: 32614373.
BibTeX
@article{margeta2020-32614373,
author = {Margeta, M. A. and Letcher, S. M. and Igo, R. P. and Cooke Bailey, J. N. and Pasquale, L. R. and Haines, J. L. and Butovsky, O. and Wiggs, J. L. and others},
title = {{Association of APOE With Primary Open-Angle Glaucoma Suggests a Protective Effect for APOE ε4}},
journal = {Investigative ophthalmology \& visual science},
year = {2020},
doi = {10.1167/iovs.61.8.3},
pmid = {32614373},
url = {https://doi.org/10.1167/iovs.61.8.3}
}
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Key findings
- Purpose Prior studies have demonstrated that microglial activation is involved in the pathogenesis of primary open-angle glaucoma (POAG).
- Here we sought to identify genetic associations between POAG and variants in APOE and TREM2, genes associated with Alzheimer disease (AD) that critically regulate microglial neurodegeneration-associated molecular signature.
- The data set was analyzed for association with POAG overall, as well as the high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) subgroups, using logistic regression adjusting for age and sex.
- Results In the combined NEIGHBOR-MEEI data set, significant association was observed for APOE ε4 in POAG overall (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.74-0.94; P = 0.0022) and in both the HTG subgroup (OR, 0.81; 95% CI, 0.70-0.94; P = 0.0052) and NTG subgroup (OR, 0.71; 95% CI, 0.58-0.87; P = 0.0014).
- Three TREM2 rare variants associated with AD were not significantly associated with POAG (P > 0.05).
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Study details
- Evidence strengthModerate
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / 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 and institution's track record, so those were left out: it earned 28 of the 61 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Investigative ophthalmology & visual science) |
| 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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32614373) |
| Free to read | 2 / 2 | Free to read |
| Points | 28 / 61 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 28 of the 61 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
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