Identifying genetic markers enriched by brain imaging endophenotypes in Alzheimer's disease
Mansu Kim, Ruiming Wu, Xiaohui Yao, Andrew J Saykin, Jason H Moore, Li Shen, Alzheimer’s Disease Neuroimaging Initiative. BMC medical genomics, 2022-08-01
Topic: Genetics and APOE
We propose a novel method to identify disease-related genetic variants enriched by imaging endophenotypes, which are the imaging traits associated with both genetic factors and disease status. Our analysis consists of three steps: (1) map the effects of a genetic variant (e.g., single nucleotide polymorphism or SNP) onto imaging traits across the brain using a linear regression model, (2) map the effects of a diagnosis phenotype onto imaging traits across the brain using a linear regression model, and (3) detect SNP-diagnosis association via correlating the SNP effects with the diagnostic effects on the brain-wide imaging traits. We demonstrate the promise of our approach by applying it to the Alzheimer's Disease Neuroimaging Initiative database. Among 54 AD related susceptibility loci reported in prior large-scale AD GWAS, our approach identifies 41 of those from a much smaller study cohort while the standard association approaches identify only two of those. Clearly, the proposed imaging endophenotype enriched approach can reveal promising AD genetic variants undetectable using the traditional method. We have proposed a novel method to identify AD genetic variants enriched by brain-wide imaging endophenotypes. This approach can not only boost detection power, but also reveal interesting biological pathways from genetic determinants to intermediate brain traits and to phenotypic AD outcomes.
Key findings
- We propose a novel method to identify disease-related genetic variants enriched by imaging endophenotypes, which are the imaging traits associated with both genetic factors and disease status.
- Our analysis consists of three steps: (1) map the effects of a genetic variant (e.g., single nucleotide polymorphism or SNP) onto imaging traits across the brain using a linear regression model, (2) map the effects of a diagnosis phenotype onto imaging traits across the brain using a linear regression model, and (3) detect SNP-diagnosis association via correlating the SNP effects with the diagnostic effects on the brain-wide imaging traits.
- We demonstrate the promise of our approach by applying it to the Alzheimer's Disease Neuroimaging Initiative database.
- Among 54 AD related susceptibility loci reported in prior large-scale AD GWAS, our approach identifies 41 of those from a much smaller study cohort while the standard association approaches identify only two of those.
- Clearly, the proposed imaging endophenotype enriched approach can reveal promising AD genetic variants undetectable using the traditional method.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designcase-control study
- Evidence strengthModerate
How this study scored 55/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for sample size, effect reported, studied in people 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, multi-centre collaboration and free to read, so those were left out: it earned 31 of the 56 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (BMC medical genomics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 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 | 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 35915443) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 31 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 31 of the 56 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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 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.
APA 7th
Kim, M., Wu, R., Yao, X., Saykin, A. J., Moore, J. H., Shen, L., et al. (2022). Identifying genetic markers enriched by brain imaging endophenotypes in Alzheimer's disease. BMC medical genomics. https://doi.org/10.1186/s12920-022-01323-8
Vancouver
Kim M, Wu R, Yao X, Saykin AJ, Moore JH, Shen L, et al. Identifying genetic markers enriched by brain imaging endophenotypes in Alzheimer's disease. BMC medical genomics. 2022. doi:10.1186/s12920-022-01323-8. PMID: 35915443.
BibTeX
@article{kim2022-35915443,
author = {Kim, Mansu and Wu, Ruiming and Yao, Xiaohui and Saykin, Andrew J and Moore, Jason H and Shen, Li and {Alzheimer’s Disease Neuroimaging Initiative}},
title = {{Identifying genetic markers enriched by brain imaging endophenotypes in Alzheimer's disease}},
journal = {BMC medical genomics},
year = {2022},
doi = {10.1186/s12920-022-01323-8},
pmid = {35915443},
url = {https://doi.org/10.1186/s12920-022-01323-8}
}
Related studies in Genetics
Also tagged “genetics”
346 studies in the library carry the topic tag “genetics”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 346 tagged studies.