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Multi-tissue neocortical transcriptome-wide association study implicates 8 genes across 6 genomic loci in Alzheimer's disease
Gockley J, Montgomery KS, Poehlman WL, Wiley JC, Liu Y, Gerasimov E, Greenwood AK, Sieberts SK et al.. Genome medicine, 2021-05-04
Topic: Amyloid, tau and blood-test diagnosis
Background Alzheimer's disease (AD) is an incurable neurodegenerative disease currently affecting 1.75% of the US population, with projected growth to 3.46% by 2050. Identifying common genetic variants driving differences in transcript expression that confer AD risk is necessary to elucidate AD mechanism and develop therapeutic interventions. We modify the FUSION transcriptome-wide association study (TWAS) pipeline to ingest gene expression values from multiple neocortical regions.
Key findings
- Identifying common genetic variants driving differences in transcript expression that confer AD risk is necessary to elucidate AD mechanism and develop therapeutic interventions.
- We modify the FUSION transcriptome-wide association study (TWAS) pipeline to ingest gene expression values from multiple neocortical regions.
- Methods A combined dataset of 2003 genotypes clustered to 1000 Genomes individuals from Utah with Northern and Western European ancestry (CEU) was used to construct a training set of 790 genotypes paired to 888 RNASeq profiles from temporal cortex (TCX = 248), prefrontal cortex (FP = 50), inferior frontal gyrus (IFG = 41), superior temporal gyrus (STG = 34), parahippocampal cortex (PHG = 34), and dorsolateral prefrontal cortex (DLPFC = 461).
- Following within-tissue normalization and covariate adjustment, predictive weights to impute expression components based on a gene's surrounding cis-variants were trained.
Why it matters
This study used a modified analysis pipeline to look at gene expression across multiple neocortical regions and implicated 8 genes across 6 genomic loci in Alzheimer's disease. It helps identify possible genetic targets for future research but does not test any treatment or cure.
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Study details
- Effect size1.75%; 3.46%; 49.67%
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Genome medicine) |
| Journal's citation record | 2 / 4 | Genome Medicine: journal h-index 174 (OpenAlex, 2026-10-29) |
| 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 | 2021 — within 6 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 63 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 4.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 41 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Benjamin A. Logsdon: h-index 36 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Emory University: institution h-index 1,360 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33947463) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
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Read the original
- DOI: 10.1186/s13073-021-00890-2
- PubMed: 33947463
- Original source →
- Free full text: Genome Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Gockley, J., Montgomery, K. S., Poehlman, W. L., Wiley, J. C., Liu, Y., Gerasimov, E., et al. (2021). Multi-tissue neocortical transcriptome-wide association study implicates 8 genes across 6 genomic loci in Alzheimer's disease. Genome medicine. https://doi.org/10.1186/s13073-021-00890-2
Vancouver
Gockley J, Montgomery KS, Poehlman WL, Wiley JC, Liu Y, Gerasimov E, et al. Multi-tissue neocortical transcriptome-wide association study implicates 8 genes across 6 genomic loci in Alzheimer's disease. Genome medicine. 2021. doi:10.1186/s13073-021-00890-2. PMID: 33947463.
BibTeX
@article{gockley2021-33947463,
author = {Gockley, J. and Montgomery, K. S. and Poehlman, W. L. and Wiley, J. C. and Liu, Y. and Gerasimov, E. and Greenwood, A. K. and Sieberts, S. K. and others},
title = {{Multi-tissue neocortical transcriptome-wide association study implicates 8 genes across 6 genomic loci in Alzheimer's disease}},
journal = {Genome medicine},
year = {2021},
doi = {10.1186/s13073-021-00890-2},
pmid = {33947463},
url = {https://doi.org/10.1186/s13073-021-00890-2}
}
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