Phenome-Wide Association Study of Polygenic Risk Score for Alzheimer's Disease in Electronic Health Records
Mingzhou Fu, UCLA Precision Health Data Discovery Repository Working Group, UCLA Precision Health ATLAS Working Group, Timothy S Chang. Frontiers in aging neuroscience, 2022-03-15
Topic: Genetics and APOE
Plain-language summary
Alzheimer's disease (AD) is the most common form of dementia and a growing public health burden in the United States. Significant progress has been made in identifying genetic risk for AD, but limited studies have investigated how AD genetic risk may be associated with other disease conditions in an unbiased fashion. In this study, we conducted a phenome-wide association study (PheWAS) by genetic ancestry groups within a large academic health system using the polygenic risk score (PRS) for AD. PRS was calculated using LDpred2 with genome-wide association study (GWAS) summary statistics. Phenotypes were extracted from electronic health record (EHR) diagnosis codes and mapped to more clinically meaningful phecodes. Logistic regression with Firth's bias correction was used for PRS phenotype analyses. Mendelian randomization was used to examine causality in significant PheWAS associations. Our results showed a strong association between AD PRS and AD phenotype in European ancestry (OR = 1.26, 95% CI: 1.13, 1.40). Among a total of 1,515 PheWAS tests within the European sample, we observed strong associations of AD PRS with AD and related phenotypes, which include mild cognitive impairment (MCI), memory loss, and dementias. We observed a phenome-wide significant association between AD PRS and gouty arthropathy (OR = 0.90, adjusted p = 0.05). Further causal inference tests with Mendelian randomization showed that gout was not causally associated with AD. We concluded that genetic predisposition of AD was negatively associated with gout, but gout was not a causal risk factor for AD. Our study evaluated AD PRS in a real-world EHR setting and provided evidence that AD PRS may help to identify individuals who are genetically at risk of AD and other related phenotypes. We identified non-neurodegenerative diseases associated with AD PRS, which is essential to understand the genetic architecture of AD and potential side effects of drugs targeting genetic risk factors of AD. Together, these findings expand our understanding of AD genetic and clinical risk factors, which provide a framework for continued research in aging with the growing number of real-world EHR linked with genetic data.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Fu, M., UCLA Precision Health Data Discovery Repository Working Group, UCLA Precision Health ATLAS Working Group, & Chang, T. S. (2022). Phenome-Wide Association Study of Polygenic Risk Score for Alzheimer's Disease in Electronic Health Records. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2022.800375
Vancouver
Fu M, UCLA Precision Health Data Discovery Repository Working Group, UCLA Precision Health ATLAS Working Group, Chang TS. Phenome-Wide Association Study of Polygenic Risk Score for Alzheimer's Disease in Electronic Health Records. Frontiers in aging neuroscience. 2022. doi:10.3389/fnagi.2022.800375. PMID: 35370621.
BibTeX
@article{fu2022-35370621,
author = {Fu, Mingzhou and {UCLA Precision Health Data Discovery Repository Working Group} and {UCLA Precision Health ATLAS Working Group} and Chang, Timothy S},
title = {{Phenome-Wide Association Study of Polygenic Risk Score for Alzheimer's Disease in Electronic Health Records}},
journal = {Frontiers in aging neuroscience},
year = {2022},
doi = {10.3389/fnagi.2022.800375},
pmid = {35370621},
url = {https://doi.org/10.3389/fnagi.2022.800375}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Significant progress has been made in identifying genetic risk for AD, but limited studies have investigated how AD genetic risk may be associated with other disease conditions in an unbiased fashion.
- Mendelian randomization was used to examine causality in significant PheWAS associations.
- Our results showed a strong association between AD PRS and AD phenotype in European ancestry (OR = 1.26, 95% CI: 1.13, 1.40).
- Among a total of 1,515 PheWAS tests within the European sample, we observed strong associations of AD PRS with AD and related phenotypes, which include mild cognitive impairment (MCI), memory loss, and dementias.
- We observed a phenome-wide significant association between AD PRS and gouty arthropathy (OR = 0.90, adjusted p = 0.05).
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Study details
- Participants1,515
- Effect sizeOR = 1.26; OR = 0.90
- Evidence strengthLow
How this study scored 57/100
Published in a peer-reviewed journal. Scored zero for study design 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, cited by studies here, still being cited, senior author's track record, institution's track record, multicenter collaboration and free to read, so those were left out: it earned 32 of the 56 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in aging neuroscience) |
| 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 | 1,515 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | — / 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35370621) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 32 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 32 of the 56 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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