Brain and Blood Transcriptome-Wide Association Studies Identify Five Novel Genes Associated with Alzheimer's Disease
Makaela A Mews, Adam C Naj, Anthony J Griswold, Alzheimer’s Disease Genetics Consortium, Jennifer E Below, William S Bush. Journal of Alzheimer's disease : JAD, 2024-04-19
Topic: Genetics and APOE
We identified and validated five novel gene associations in cortical brain tissue ( PRKAG1 , C3orf62 , LYSMD4 , ZNF439 , SLC11A2 ) and six genes proximal to known AD-related GWAS loci (Blood: MYBPC3 ; Brain: MTCH2 , CYB561 , MADD , PSMA5 , ANXA11 ). Further, using causal eQTL fine-mapping, we generated sparse models that retained the strength of the AD-TWAS association for MTCH2 , MADD , ZNF439 , CYB561 , and MYBPC3 . Our comprehensive AD-TWAS discovered new gene associations and provided insights into the functional relevance of previously associated variants.
Key findings
- We identified and validated five novel gene associations in cortical brain tissue ( PRKAG1 , C3orf62 , LYSMD4 , ZNF439 , SLC11A2 ) and six genes proximal to known AD-related GWAS loci (Blood: MYBPC3 ; Brain: MTCH2 , CYB561 , MADD , PSMA5 , ANXA11 ).
- Further, using causal eQTL fine-mapping, we generated sparse models that retained the strength of the AD-TWAS association for MTCH2 , MADD , ZNF439 , CYB561 , and MYBPC3 .
- Our comprehensive AD-TWAS discovered new gene associations and provided insights into the functional relevance of previously associated variants.
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Study details
- Study designmeta-analysis
- Participants2,683
- Evidence strengthHigh
How this study scored 82/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported 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, multi-centre collaboration and free to read, so those were left out: it earned 46 of the 56 points we could judge it on, which is 82 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| 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 | 3 / 4 | 2,683 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 | 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 38699333) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 46 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 46 of the 56 points we could judge it on is 82 out of 100. |
| Total | 82 / 100 | — |
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APA 7th
Mews, M. A., Naj, A. C., Griswold, A. J., Alzheimer’s Disease Genetics Consortium, Below, J. E., & Bush, W. S. (2024). Brain and Blood Transcriptome-Wide Association Studies Identify Five Novel Genes Associated with Alzheimer's Disease. Journal of Alzheimer's disease : JAD. https://doi.org/10.1101/2024.04.17.24305737
Vancouver
Mews MA, Naj AC, Griswold AJ, Alzheimer’s Disease Genetics Consortium, Below JE, Bush WS. Brain and Blood Transcriptome-Wide Association Studies Identify Five Novel Genes Associated with Alzheimer's Disease. Journal of Alzheimer's disease : JAD. 2024. doi:10.1101/2024.04.17.24305737. PMID: 38699333.
BibTeX
@article{mews2024-38699333,
author = {Mews, Makaela A and Naj, Adam C and Griswold, Anthony J and {Alzheimer’s Disease Genetics Consortium} and Below, Jennifer E and Bush, William S},
title = {{Brain and Blood Transcriptome-Wide Association Studies Identify Five Novel Genes Associated with Alzheimer's Disease}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2024},
doi = {10.1101/2024.04.17.24305737},
pmid = {38699333},
url = {https://doi.org/10.1101/2024.04.17.24305737}
}