Shared genetic contribution to Ischaemic Stroke and Alzheimer's Disease
Traylor M, Adib-Samii P, Harold D, Alzheimer's Disease Neuroimaging Initiative, International Stroke Genetics Consortium (ISGC), UK Young Lacunar Stroke DNA resource, Dichgans M, Williams J et al.. Annals of neurology, 2016-02-23
Topic: Amyloid, tau and blood-test diagnosis
Objective Increasing evidence suggests epidemiological and pathological links between Alzheimer's disease (AD) and Ischaemic Stroke (IS). We investigated the evidence that shared genetic factors underpin the two diseases. Methods Using genome wide association study (GWAS) data from METASTROKE+ (15,916 IS cases and 68,826 controls) and IGAP (17,008 AD cases and 37,154 controls), we evaluated known associations with AD and IS. On the subset of data for which we could obtain compatible genotype-level data (4,610 IS cases, 1,281 AD cases and 14,320 controls), we estimated the genome-wide genetic correlation (rG) between AD and IS, and the three subtypes (cardioembolic, small vessel, large vessel), using genome-wide SNP data. We then performed a meta-analysis and pathway analysis in the combined AD and small vessel stroke datasets to identify the SNPs and molecular pathways through which disease risk may be conferred. Results We found evidence of a shared genetic contribution between AD and small vessel stroke (rG(SE)=0.37(0.17); p=0.011). Conversely, there was no evidence to support shared genetic factors in AD and IS overall, or with the other stroke subtypes. Of the known GWAS associations with IS or AD, none reached significance for association with the other trait (or stroke subtypes). A meta-analysis of AD IGAP and METASTROKE+ small vessel stroke GWAS data highlighted a region (ATP5H/KCTD2/ICT1), associated with both diseases (p=1.8x10 -8 ). A pathway analysis identified four associated pathways, involving cholesterol transport and immune response. Interpretation Our findings indicate shared genetic susceptibility to AD and small vessel stroke and highlight potential causal pathways and loci. This article is protected by copyright. All rights reserved.
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APA 7th
Traylor, M., Adib-Samii, P., Harold, D., Alzheimer's Disease Neuroimaging Initiative, resource, U. K. Y. L. S. D. N. A., Dichgans, M., et al. (2016). Shared genetic contribution to Ischaemic Stroke and Alzheimer's Disease. Annals of neurology. https://doi.org/10.1002/ana.24621
Vancouver
Traylor M, Adib-Samii P, Harold D, Alzheimer's Disease Neuroimaging Initiative, resource UKYLSDNA, Dichgans M, et al. Shared genetic contribution to Ischaemic Stroke and Alzheimer's Disease. Annals of neurology. 2016. doi:10.1002/ana.24621. PMID: 26913989.
BibTeX
@article{traylor2016-26913989,
author = {Traylor, M. and Adib-Samii, P. and Harold, D. and {Alzheimer's Disease Neuroimaging Initiative} and resource, UK Young Lacunar Stroke DNA and Dichgans, M. and Williams, J. and others},
title = {{Shared genetic contribution to Ischaemic Stroke and Alzheimer's Disease}},
journal = {Annals of neurology},
year = {2016},
doi = {10.1002/ana.24621},
pmid = {26913989},
url = {https://doi.org/10.1002/ana.24621}
}
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Key findings
- Results We found evidence of a shared genetic contribution between AD and small vessel stroke (rG(SE)=0.37(0.17); p=0.011).
- Conversely, there was no evidence to support shared genetic factors in AD and IS overall, or with the other stroke subtypes.
- A meta-analysis of AD IGAP and METASTROKE+ small vessel stroke GWAS data highlighted a region (ATP5H/KCTD2/ICT1), associated with both diseases (p=1.8x10 -8 ).
- Interpretation Our findings indicate shared genetic susceptibility to AD and small vessel stroke and highlight potential causal pathways and loci.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 71/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people 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 41 of the 58 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| 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 | 1 / 5 | 2016 — within 20 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 | 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 26913989) |
| Free to read | 2 / 2 | Free to read |
| Points | 41 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 41 of the 58 points we could judge it on is 71 out of 100. |
| Total | 71 / 100 | — |
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