Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease
Wu Y, Sun Z, Zheng Q, Miao J, Dorn S, Mukherjee S, Fletcher JM, Lu Q.. Nature genetics, 2024-11-04
Topic: Amyloid, tau and blood-test diagnosis
Almost every recent Alzheimer's disease (AD) genome-wide association study (GWAS) has performed meta-analysis to combine studies with clinical diagnosis of AD with studies that use proxy phenotypes based on parental disease history. Here, we report major limitations in current GWAS-by-proxy (GWAX) practices due to uncorrected survival bias and nonrandom participation in parental illness surveys, which cause substantial discrepancies between AD GWAS and GWAX results. We demonstrate that the current AD GWAX provide highly misleading genetic correlations between AD risk and higher education, which subsequently affects a variety of genetic epidemiological applications involving AD and cognition. Our study sheds light on potential issues in the design and analysis of middle-aged biobank cohorts and underscores the need for caution when interpreting genetic association results based on proxy-reported parental disease history.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wu, Y., Sun, Z., Zheng, Q., Miao, J., Dorn, S., Mukherjee, S., et al. (2024). Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease. Nature genetics. https://doi.org/10.1038/s41588-024-01963-9
Vancouver
Wu Y, Sun Z, Zheng Q, Miao J, Dorn S, Mukherjee S, et al. Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease. Nature genetics. 2024. doi:10.1038/s41588-024-01963-9. PMID: 39496879.
BibTeX
@article{wu2024-39496879,
author = {Wu, Y. and Sun, Z. and Zheng, Q. and Miao, J. and Dorn, S. and Mukherjee, S. and Fletcher, J. M. and Lu, Q.},
title = {{Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease}},
journal = {Nature genetics},
year = {2024},
doi = {10.1038/s41588-024-01963-9},
pmid = {39496879},
url = {https://doi.org/10.1038/s41588-024-01963-9}
}
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Key findings
- Here, we report major limitations in current GWAS-by-proxy (GWAX) practices due to uncorrected survival bias and nonrandom participation in parental illness surveys, which cause substantial discrepancies between AD GWAS and GWAX results.
- Our study sheds light on potential issues in the design and analysis of middle-aged biobank cohorts and underscores the need for caution when interpreting genetic association results based on proxy-reported parental disease history.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 72/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people 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 (Nature genetics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 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 | A review of other studies — randomisation is not credited here |
| 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 39496879) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| 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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