Home › Research › Risk genes beyond APOE
Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2
Simon Hsu, Anna A Pimenova, Kimberly Hayes, Juan A Villa, Matthew J Rosene, Madhavi Jere, Alison M Goate, Celeste M Karch. Neurobiology of disease, 2020-02-19
Topic: Genetics and APOE
Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. More than 200 pathogenic mutations have been identified in amyloid-β precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Additionally, common and rare variants occur within APP, PSEN1, and PSEN2 that may be risk factors, protective factors, or benign, non-pathogenic polymorphisms. Yet, to date, no single study has carefully examined the effect of all of the variants of unknown significance reported in APP, PSEN1 and PSEN2 on Aβ isoform levels in vitro. In this study, we analyzed Aβ isoform levels by ELISA in a cell-based system in which each reported pathogenic and risk variant in APP, PSEN1, and PSEN2 was expressed individually. In order to classify variants for which limited family history data is available, we have implemented an algorithm for determining pathogenicity using available information from multiple domains, including genetic, bioinformatic, and in vitro analyses. We identified 90 variants of unknown significance and classified 19 as likely pathogenic mutations. We also propose that five variants are possibly protective. In defining a subset of these variants as pathogenic, individuals from these families may eligible to enroll in observational studies and clinical trials.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Hsu, S., Pimenova, A. A., Hayes, K., Villa, J. A., Rosene, M. J., Jere, M., et al. (2020). Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2. Neurobiology of disease. https://doi.org/10.1016/j.nbd.2020.104817
Vancouver
Hsu S, Pimenova AA, Hayes K, Villa JA, Rosene MJ, Jere M, et al. Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2. Neurobiology of disease. 2020. doi:10.1016/j.nbd.2020.104817. PMID: 32087291.
BibTeX
@article{hsu2020-32087291,
author = {Hsu, Simon and Pimenova, Anna A and Hayes, Kimberly and Villa, Juan A and Rosene, Matthew J and Jere, Madhavi and Goate, Alison M and Karch, Celeste M},
title = {{Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2}},
journal = {Neurobiology of disease},
year = {2020},
doi = {10.1016/j.nbd.2020.104817},
pmid = {32087291},
url = {https://doi.org/10.1016/j.nbd.2020.104817}
}
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- In this study, we analyzed Aβ isoform levels by ELISA in a cell-based system in which each reported pathogenic and risk variant in APP, PSEN1, and PSEN2 was expressed individually.
- In order to classify variants for which limited family history data is available, we have implemented an algorithm for determining pathogenicity using available information from multiple domains, including genetic, bioinformatic, and in vitro analyses.
- We identified 90 variants of unknown significance and classified 19 as likely pathogenic mutations.
- We also propose that five variants are possibly protective.
- In defining a subset of these variants as pathogenic, individuals from these families may eligible to enroll in observational studies and clinical trials.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 39/100
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, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 22 of the 56 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of disease) |
| 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 | 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 | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32087291) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 22 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 22 of the 56 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Risk genes beyond APOE
Also tagged “genetics”
346 studies in the library carry the topic tag “genetics”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 346 tagged studies.