Common genetic variants associated with cognitive performance identified using the proxy-phenotype method
Rietveld CA, Esko T, Davies G, Pers TH, Turley P, Benyamin B, Chabris CF, Emilsson V et al.. Proceedings of the National Academy of Sciences of the United States of America, 2014-09-08
Topic: Genetics and APOE
We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.
Key findings
- We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method.
- Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing.
- In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia.
- All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.
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Study details
- Participants106,736
- Evidence strengthLow
How this study scored 69/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported 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 40 of the 58 points we could judge it on, which is 69 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| 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 (from PubMed type “Meta-Analysis”) |
| 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 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 4 / 4 | 106,736 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) |
| 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 25201988) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 40 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 40 of the 58 points we could judge it on is 69 out of 100. |
| Total | 69 / 100 | — |
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APA 7th
Rietveld, C. A., Esko, T., Davies, G., Pers, T. H., Turley, P., Benyamin, B., et al. (2014). Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1404623111
Vancouver
Rietveld CA, Esko T, Davies G, Pers TH, Turley P, Benyamin B, et al. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. Proceedings of the National Academy of Sciences of the United States of America. 2014. doi:10.1073/pnas.1404623111. PMID: 25201988.
BibTeX
@article{rietveld2014-25201988,
author = {Rietveld, C. A. and Esko, T. and Davies, G. and Pers, T. H. and Turley, P. and Benyamin, B. and Chabris, C. F. and Emilsson, V. and others},
title = {{Common genetic variants associated with cognitive performance identified using the proxy-phenotype method}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2014},
doi = {10.1073/pnas.1404623111},
pmid = {25201988},
url = {https://doi.org/10.1073/pnas.1404623111}
}