Shared genetic etiology underlying Alzheimer's disease and major depressive disorder
Lutz MW, Sprague D, Barrera J, Chiba-Falek O.. Translational psychiatry, 2020-03-09
Topic: Amyloid, tau and blood-test diagnosis
Patients with late-onset Alzheimer's disease (LOAD) frequently manifest comorbid neuropsychiatric symptoms with depression and anxiety being most frequent, and individuals with major depressive disorder (MDD) have an increased prevalence of LOAD. This suggests shared etiologies and intersecting pathways between LOAD and MDD. We performed pleiotropy analyses using LOAD and MDD GWAS data sets from the International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium (PGC), respectively. We found a moderate enrichment for SNPs associated with LOAD across increasingly stringent levels of significance with the MDD GWAS association (LOAD|MDD), of maximum four and eightfolds, including and excluding the APOE-region, respectively. Association analysis excluding the APOE-region identified numerous SNPs corresponding to 40 genes, 9 of which are known LOAD-risk loci primarily in chromosome 11 regions that contain the SPI1 gene and MS4A genes cluster, and others were novel pleiotropic risk-loci for LOAD conditional with MDD. The most significant associated SNPs on chromosome 11 overlapped with eQTLs found in whole-blood and monocytes, suggesting functional roles in gene regulation. The reverse conditional association analysis (MDD|LOAD) showed a moderate level, ~sevenfold, of polygenic overlap, however, no SNP showed significant association. Pathway analyses replicated previously reported LOAD biological pathways related to immune response and regulation of endocytosis. In conclusion, we provide insights into the overlapping genetic signatures underpinning the common phenotypic manifestations and inter-relationship between LOAD and MDD. This knowledge is crucial to the development of actionable targets for novel therapies to treat depression preceding dementia, in an effort to delay or ultimately prevent the onset of LOAD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Lutz, M. W., Sprague, D., Barrera, J., & Chiba-Falek, O. (2020). Shared genetic etiology underlying Alzheimer's disease and major depressive disorder. Translational psychiatry. https://doi.org/10.1038/s41398-020-0769-y
Vancouver
Lutz MW, Sprague D, Barrera J, Chiba-Falek O. Shared genetic etiology underlying Alzheimer's disease and major depressive disorder. Translational psychiatry. 2020. doi:10.1038/s41398-020-0769-y. PMID: 32152295.
BibTeX
@article{lutz2020-32152295,
author = {Lutz, M. W. and Sprague, D. and Barrera, J. and Chiba-Falek, O.},
title = {{Shared genetic etiology underlying Alzheimer's disease and major depressive disorder}},
journal = {Translational psychiatry},
year = {2020},
doi = {10.1038/s41398-020-0769-y},
pmid = {32152295},
url = {https://doi.org/10.1038/s41398-020-0769-y}
}
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
- We found a moderate enrichment for SNPs associated with LOAD across increasingly stringent levels of significance with the MDD GWAS association (LOAD|MDD), of maximum four and eightfolds, including and excluding the APOE-region, respectively.
- The most significant associated SNPs on chromosome 11 overlapped with eQTLs found in whole-blood and monocytes, suggesting functional roles in gene regulation.
- The reverse conditional association analysis (MDD|LOAD) showed a moderate level, ~sevenfold, of polygenic overlap, however, no SNP showed significant association.
- In conclusion, we provide insights into the overlapping genetic signatures underpinning the common phenotypic manifestations and inter-relationship between LOAD and MDD.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, 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 and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Translational psychiatry) |
| 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 | 2 / 5 | 2020 — within 10 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 32152295) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 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.
Related studies in Genetics
Also tagged “genetic-etiology”
3 studies in the library carry the topic tag “genetic-etiology”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 3 tagged studies.