Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium
Debette S, Ibrahim Verbaas CA, Bressler J, Schuur M, Smith A, Bis JC, Davies G, Wolf C et al.. Biological psychiatry, 2014-11-25
Topic: Risk, prevention and care in population studies
Background Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. Methods We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. Results rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. Conclusions This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.
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APA 7th
Debette, S., Ibrahim Verbaas, C. A., Bressler, J., Schuur, M., Smith, A., Bis, J. C., et al. (2015). Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Biological psychiatry. https://doi.org/10.1016/j.biopsych.2014.08.027
Vancouver
Debette S, Ibrahim Verbaas CA, Bressler J, Schuur M, Smith A, Bis JC, et al. Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Biological psychiatry. 2015. doi:10.1016/j.biopsych.2014.08.027. PMID: 25648963.
BibTeX
@article{debette2015-25648963,
author = {Debette, S. and Ibrahim Verbaas, C. A. and Bressler, J. and Schuur, M. and Smith, A. and Bis, J. C. and Davies, G. and Wolf, C. and others},
title = {{Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium}},
journal = {Biological psychiatry},
year = {2015},
doi = {10.1016/j.biopsych.2014.08.027},
pmid = {25648963},
url = {https://doi.org/10.1016/j.biopsych.2014.08.027}
}
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Key findings
- Results rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)).
- A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples.
- Conclusions This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.
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Study details
- Participants10,617
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / 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 multicenter collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biological 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 | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 4 / 4 | 10,617 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25648963) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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