Topic: Amyloid, tau and blood-test diagnosis
The heritability of Alzheimer's disease estimated from twin studies is greater than the heritability derived from genome-based studies, for reasons that remain unclear. We apply both approaches to the same twin sample, considering both Alzheimer's disease polygenic risk scores and heritability from twin models, to provide insight into the role of measured genetic variants and to quantify uncaptured genetic risk. A population-based heritability and polygenic association study of Alzheimer's disease was conducted between 1986 and 2016 and is the first study to incorporate polygenic risk scores into biometrical twin models of Alzheimer's disease. The sample included 1586 twins drawn from the Swedish Twin Registry which were nested within 1137 twin pairs (449 complete pairs and 688 incomplete pairs) with clinically based diagnoses and registry follow-up ( M age = 85.28, SD = 7.02; 44% male; 431 cases and 1155 controls). We report contributions of polygenic risk scores at P < 1 × 10 -5 , considering a full polygenic risk score (PRS), PRS without the APOE region (PRS.no.APOE) and PRS.no.APOE plus directly measured APOE alleles. Biometric twin models estimated the contribution of environmental influences and measured (PRS) and unmeasured genes to Alzheimer's disease risk. The full PRS and PRS.no.APOE contributed 10.1 and 2.4% to Alzheimer's disease risk, respectively. When APOE ɛ4 alleles were added to the model with the PRS.no.APOE, the total contribution was 11.4% to Alzheimer's disease risk, where APOE ɛ4 explained 9.3% and PRS.no.APOE dropped from 2.4 to 2.1%. The total genetic contribution to Alzheimer's disease risk, measured and unmeasured, was 71% while environmental influences unique to each twin accounted for 29% of the risk. The APOE region accounts for much of the measurable genetic contribution to Alzheimer's disease, with a smaller contribution from other measured polygenic influences. Importantly, substantial background genetic influences remain to be understood.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Karlsson, I. K., Escott-Price, V., Gatz, M., Hardy, J., Pedersen, N. L., Shoai, M., et al. (2022). Measuring heritable contributions to Alzheimer's disease: polygenic risk score analysis with twins. Brain communications. https://doi.org/10.1093/braincomms/fcab308
Vancouver
Karlsson IK, Escott-Price V, Gatz M, Hardy J, Pedersen NL, Shoai M, et al. Measuring heritable contributions to Alzheimer's disease: polygenic risk score analysis with twins. Brain communications. 2022. doi:10.1093/braincomms/fcab308. PMID: 35169705.
BibTeX
@article{karlsson2022-35169705,
author = {Karlsson, I. K. and Escott-Price, V. and Gatz, M. and Hardy, J. and Pedersen, N. L. and Shoai, M. and Reynolds, C. A.},
title = {{Measuring heritable contributions to Alzheimer's disease: polygenic risk score analysis with twins}},
journal = {Brain communications},
year = {2022},
doi = {10.1093/braincomms/fcab308},
pmid = {35169705},
url = {https://doi.org/10.1093/braincomms/fcab308}
}
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 7 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
- The full PRS and PRS.no.APOE contributed 10.1 and 2.4% to Alzheimer's disease risk, respectively.
- When APOE ɛ4 alleles were added to the model with the PRS.no.APOE, the total contribution was 11.4% to Alzheimer's disease risk, where APOE ɛ4 explained 9.3% and PRS.no.APOE dropped from 2.4 to 2.1%.
- The total genetic contribution to Alzheimer's disease risk, measured and unmeasured, was 71% while environmental influences unique to each twin accounted for 29% of the risk.
- The APOE region accounts for much of the measurable genetic contribution to Alzheimer's disease, with a smaller contribution from other measured polygenic influences.
- Importantly, substantial background genetic influences remain to be understood.
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Study details
- Participants1,586
- Effect size2.4%; 11.4%; 9.3%
- Evidence strengthLow
How this study scored 60/100
Published in a leading specialty journal. Scored zero for study design 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 35 of the 58 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain communications) |
| 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 | 3 / 4 | 1,586 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 35169705) |
| Free to read | 2 / 2 | Free to read |
| Points | 35 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 35 of the 58 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
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