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Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory
Cannon TD, Hennah W, van Erp TG, Thompson PM, Lonnqvist J, Huttunen M, Gasperoni T, Tuulio-Henriksson A et al.. Archives of general psychiatry, 2005-11-01
Topic: Brain proteins, microglia and lab models
Context Chromosome 1q42 is among several genomic regions showing replicated evidence of linkage with schizophrenia, but the specific susceptibility mechanisms underlying this relationship remain to be identified. Objective To examine a series of haplotype blocks of single-nucleotide polymorphic markers from a segment of 1q42 spanning the disrupted-in-schizophrenia 1 (DISC1) and translin-associated factor X (TRAX) genes for association with schizophrenia and several endophenotypic traits thought to be involved in disease pathogenesis. Design Population-based twin cohort study. Setting Finland. Participants Two hundred thirty-six subjects, consisting of 7 twin pairs concordant for schizophrenia (6 monozygotic [MZ] and 1 dizygotic [DZ]), 52 pairs discordant for schizophrenia (20 MZ and 32 DZ), and 59 demographically balanced normal pairs (28 MZ and 31 DZ), were drawn from a twin cohort consisting of all of the same-sex twins born in Finland from 1940 through 1957. Main outcome measures Psychiatric diagnosis, performance on neurocognitive tests of short- and long-term memory, and gray matter volume measurements taken from high-resolution magnetic resonance images. Results A common haplotype incorporating 3 single-nucleotide polymorphic markers near the translocation break point of DISC1 (odds ratio, 2.6 [P = .02]) and a rare haplotype incorporating 4 markers from the DISC1 and TRAX genes (odds ratio, 13.0 [P = .001]) were significantly overrepresented among individuals with schizophrenia. These haplotypes were also associated with several quantitative endophenotypic traits previously observed to covary with schizophrenia and genetic liability to schizophrenia, including impairments in short- and long-term memory functioning and reduced gray matter density in the prefrontal cortex, as demonstrated using a population-based brain atlas method, with a trend toward association with reduced hippocampal volume. Conclusions Specific alleles of the DISC1 and TRAX genes on 1q42 appear to contribute to genetic risk for schizophrenia through disruptive effects on the structure and function of the prefrontal cortex, medial temporal lobe, and other brain regions. These effects are consistent with their production of proteins that play roles in neuritic outgrowth, neuronal migration, synaptogenesis, and glutamatergic neurotransmission.
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APA 7th
Cannon, T. D., Hennah, W., van Erp, T. G., Thompson, P. M., Lonnqvist, J., Huttunen, M., et al. (2005). Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of general psychiatry. https://doi.org/10.1001/archpsyc.62.11.1205
Vancouver
Cannon TD, Hennah W, van Erp TG, Thompson PM, Lonnqvist J, Huttunen M, et al. Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of general psychiatry. 2005. doi:10.1001/archpsyc.62.11.1205. PMID: 16275808.
BibTeX
@article{cannon2005-16275808,
author = {Cannon, T. D. and Hennah, W. and van Erp, T. G. and Thompson, P. M. and Lonnqvist, J. and Huttunen, M. and Gasperoni, T. and Tuulio-Henriksson, A. and others},
title = {{Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory}},
journal = {Archives of general psychiatry},
year = {2005},
doi = {10.1001/archpsyc.62.11.1205},
pmid = {16275808},
url = {https://doi.org/10.1001/archpsyc.62.11.1205}
}
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Key findings
- Results A common haplotype incorporating 3 single-nucleotide polymorphic markers near the translocation break point of DISC1 (odds ratio, 2.6 [P = .02]) and a rare haplotype incorporating 4 markers from the DISC1 and TRAX genes (odds ratio, 13.0 [P = .001]) were significantly overrepresented among individuals with schizophrenia.
- These haplotypes were also associated with several quantitative endophenotypic traits previously observed to covary with schizophrenia and genetic liability to schizophrenia, including impairments in short- and long-term memory functioning and reduced gray matter density in the prefrontal cortex, as demonstrated using a population-based brain atlas method, with a trend toward association with reduced hippocampal volume.
Study details
- Study designcohort study
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for sample size, 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 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of general psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2005 — older than 20 years, still counted |
| 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| 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 16275808) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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