Age-Dependent Pleiotropy Between General Cognitive Function and Major Psychiatric Disorders
Hill WD, Davies G, CHARGE Cognitive Working Group, Liewald DC, McIntosh AM, Deary IJ.. Biological psychiatry, 2015-09-04
Topic: Risk, prevention and care in population studies
Background General cognitive function predicts psychiatric illness across the life course. This study examines the role of pleiotropy in explaining the link between cognitive function and psychiatric disorder. Methods We used two large genome-wide association study data sets on cognitive function-one from older age, n = 53,949, and one from childhood, n = 12,441. We also used genome-wide association study data on educational attainment, n = 95,427, to examine the validity of its use as a proxy phenotype for cognitive function. Using a new method, linkage disequilibrium regression, we derived genetic correlations, free from the confounding of clinical state between psychiatric illness and cognitive function. Results We found a genetic correlation of .711 (p = 2.26e-12) across the life course for general cognitive function. We also showed a positive genetic correlation between autism spectrum disorder and cognitive function in childhood (rg = .360, p = .0009) and for educational attainment (rg = .322, p = 1.37e-5) but not in older age. In schizophrenia, we found a negative genetic correlation between older age cognitive function (rg = -.231, p = 3.81e-12) but not in childhood or for educational attainment. For Alzheimer's disease, we found negative genetic correlations with childhood cognitive function (rg = -.341, p = .001), educational attainment (rg = -.324, p = 1.15e-5), and with older age cognitive function (rg = -.324, p = 1.78e-5). Conclusions The pleiotropy exhibited between cognitive function and psychiatric disorders changed across the life course. These age-dependent associations might explain why negative selection has not removed variants causally associated with autism spectrum disorder or schizophrenia.
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APA 7th
Hill, W. D., Davies, G., CHARGE Cognitive Working Group, Liewald, D. C., McIntosh, A. M., & Deary, I. J. (2016). Age-Dependent Pleiotropy Between General Cognitive Function and Major Psychiatric Disorders. Biological psychiatry. https://doi.org/10.1016/j.biopsych.2015.08.033
Vancouver
Hill WD, Davies G, CHARGE Cognitive Working Group, Liewald DC, McIntosh AM, Deary IJ. Age-Dependent Pleiotropy Between General Cognitive Function and Major Psychiatric Disorders. Biological psychiatry. 2016. doi:10.1016/j.biopsych.2015.08.033. PMID: 26476593.
BibTeX
@article{hill2016-26476593,
author = {Hill, W. D. and Davies, G. and {CHARGE Cognitive Working Group} and Liewald, D. C. and McIntosh, A. M. and Deary, I. J.},
title = {{Age-Dependent Pleiotropy Between General Cognitive Function and Major Psychiatric Disorders}},
journal = {Biological psychiatry},
year = {2016},
doi = {10.1016/j.biopsych.2015.08.033},
pmid = {26476593},
url = {https://doi.org/10.1016/j.biopsych.2015.08.033}
}
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Key findings
- Results We found a genetic correlation of .711 (p = 2.26e-12) across the life course for general cognitive function.
- In schizophrenia, we found a negative genetic correlation between older age cognitive function (rg = -.231, p = 3.81e-12) but not in childhood or for educational attainment.
- For Alzheimer's disease, we found negative genetic correlations with childhood cognitive function (rg = -.341, p = .001), educational attainment (rg = -.324, p = 1.15e-5), and with older age cognitive function (rg = -.324, p = 1.78e-5).
- These age-dependent associations might explain why negative selection has not removed variants causally associated with autism spectrum disorder or schizophrenia.
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Study details
- Participants53,949
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported 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 30 of the 58 points we could judge it on, which is 52 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 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 4 / 4 | 53,949 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 | 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 26476593) |
| Free to read | 2 / 2 | Free to read |
| Points | 30 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 30 of the 58 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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