Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study
Jia L, Li F, Wei C, Zhu M, Qu Q, Qin W, Tang Y, Shen L et al.. Brain : a journal of neurology, 2021-04-01
Topic: Amyloid, tau and blood-test diagnosis
Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer's disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer's disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer's disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10-19, 2.49 × 10-23, 1.35 × 10-67, and 4.81 × 10-9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10-8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer's disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer's disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.
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APA 7th
Jia, L., Li, F., Wei, C., Zhu, M., Qu, Q., Qin, W., et al. (2021). Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study. Brain : a journal of neurology. https://doi.org/10.1093/brain/awaa364
Vancouver
Jia L, Li F, Wei C, Zhu M, Qu Q, Qin W, et al. Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study. Brain : a journal of neurology. 2021. doi:10.1093/brain/awaa364. PMID: 33188687.
BibTeX
@article{jia2021-33188687,
author = {Jia, L. and Li, F. and Wei, C. and Zhu, M. and Qu, Q. and Qin, W. and Tang, Y. and Shen, L. and others},
title = {{Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study}},
journal = {Brain : a journal of neurology},
year = {2021},
doi = {10.1093/brain/awaa364},
pmid = {33188687},
url = {https://doi.org/10.1093/brain/awaa364}
}
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Key findings
- Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis.
- These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages.
- The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility.
- In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population.
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Study details
- Study designlongitudinal study
- Participants3,913
- Evidence strengthModerate
How this study scored 72/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported 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 and multi-centre collaboration, so those were left out: it earned 42 of the 58 points we could judge it on, which is 72 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 3,913 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 | 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 33188687) |
| Free to read | 2 / 2 | Free to read |
| Points | 42 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 42 of the 58 points we could judge it on is 72 out of 100. |
| Total | 72 / 100 | — |
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