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Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development
Prokopenko Dmitry, Morgan Sarah L, Mullin Kristina, Hofmann Oliver, Chapman Brad, Kirchner Rory, Amberkar Sandeep, Wohlers Inken et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2020-11-12
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Genome-wide association studies have led to numerous genetic loci associated with Alzheimer's disease (AD). Whole-genome sequencing (WGS) now permit genome-wide analyses to identify rare variants contributing to AD risk. We performed single-variant and spatial clustering-based testing on rare variants (minor allele frequency ≤1%) in a family-based WGS-based association study of 2,247 subjects from 605 multiplex AD families, followed by replication in 1,669 unrelated individuals. We identified 13 new AD candidate loci that yielded consistent rare-variant signals in discovery and replication cohorts (4 from single-variant, 9 from spatial-clustering), implicating these genes: FNBP1L, SEL1L, LINC00298, PRKCH, C15ORF41, C2CD3, KIF2A, APC, LHX9, NALCN, CTNNA2, SYTL3, CLSTN2. Downstream analyses of these novel loci highlight synaptic function, in contrast to common AD-associated variants, which implicate innate immunity. These loci have not been previously associated with AD, emphasizing the ability of WGS to identify AD-associated rare variants, particularly outside of coding regions.
What this study adds
Evidence grade: Low
The record lists 2,247 participants. Using whole-genome sequencing in families with multiple Alzheimer's cases, this study identified 13 new candidate genes, many related to synaptic function. These are genetic associations that may guide future research, not a treatment or cure.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Dmitry, P., Morgan Sarah, L., Kristina, M., Oliver, H., Brad, C., Rory, K., et al. (2020). Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1101/2020.11.03.20225540
Vancouver
Dmitry P, Morgan Sarah L, Kristina M, Oliver H, Brad C, Rory K, et al. Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2020. doi:10.1101/2020.11.03.20225540. PMID: 33173892.
BibTeX
@article{dmitry2020-33173892,
author = {Dmitry, Prokopenko and Morgan Sarah, L. and Kristina, Mullin and Oliver, Hofmann and Brad, Chapman and Rory, Kirchner and Sandeep, Amberkar and Inken, Wohlers and others},
title = {{Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2020},
doi = {10.1101/2020.11.03.20225540},
pmid = {33173892},
url = {https://doi.org/10.1101/2020.11.03.20225540}
}
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.
Key findings
- Genome-wide association studies have led to numerous genetic loci associated with Alzheimer's disease (AD).
- These loci have not been previously associated with AD, emphasizing the ability of WGS to identify AD-associated rare variants, particularly outside of coding regions.
Why it matters
Using whole-genome sequencing in families with multiple Alzheimer's cases, this study identified 13 new candidate genes, many related to synaptic function. These are genetic associations that may guide future research, not a treatment or cure.
New to this subject? Start with our plain-English guide: Risk factors, ranked →
Study details
- Participants2,247
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty 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, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 31 of the 64 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | 3 / 4 | 2,247 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 | 1 / 6 | Cited by 2 other studies in this library |
| 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 33797837) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 64 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 31 of the 64 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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