Repeat sizes at CAG/CTG loci CTG18.1, ERDA1 and TGC13-7a in schizophrenia

Bowen, Timothy; Guy, Carol; Cardno, A. G.; Vincent, J.; Kennedy, John; Jones, L. A.; Gray, Maryke; Sanders, Rhys; McCarthy, Geraldine; Murphy, K. C.; O'Donovan, Michael Conlon

doi:10.1097/00041444-200010010-00006

Cited by 11 publications

(8 citation statements)

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“…In our study, less than 70% of genomic CAG/CTG corresponded with these sites, suggesting the possibility of pathogenic expansions in schizophrenia at a different locus. This is comparable with Bowen et al [4] findings. They combined UK and North-American data, and found that 54% of CAG/CTG repeats larger than 40 can be accounted for CTG18.1, ERDA1 and an additional locus with non-pathogenic repeats, TGC13-7a.…”

Section: Discussionsupporting

confidence: 92%

Early development and unstable genes in schizophrenia: preliminary results

Ayton

Morris²,

Tyson

et al. 2002

Eur. psychiatr.

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Section: Discussionsupporting

confidence: 92%

Early development and unstable genes in schizophrenia: preliminary results

Ayton

Morris²,

Tyson

et al. 2002

Eur. psychiatr.

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“…Expansions as long as thousands of repeats are present in about 3% of the population. Most [Guy et al, 1999; Vincent et al, 1999; Bowen et al, 2000; McInnis et al, 2000; Meira‐Lima et al, 2001], though not all [Del Favero et al, 2002], evidence suggests that CTG18.1 expansion is not associated with a psychiatric phenotype. Southern blots of EcoR1 digested DNA using a probe flanking the repeat demonstrated that CTG 18.1 could account for 7 of the 8 Dir‐1 negative RED expansions in our sample of schizophrenia patients (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The RED assay itself provides no information about flanking sequence or the location of the repeat; however, it has been used in conjunction with other molecular techniques to find the specific repeat expansion responsible for four different disorders [Koob et al, 1998, 1999; Holmes et al, 1999, 2001]. Intriguingly, at least two groups have reported that between 48% and 66% of CAG/CTG repeat expansions detected by RED in schizophrenia, bipolar, or control populations could not be explained by any of the repeats known to undergo expansion [Guy et al, 1999; Vincent et al, 1999; Bowen et al, 2000], suggesting that currently unidentified CAG/CTG repeat expansions could contribute to the risk of bipolar disorder or schizophrenia. To explore this possibility, we used RED to identify CAG/CTG repeat expansions in 100 unrelated probands with schizophrenia and 68 probands with bipolar affective disorder, all ascertained in the United States.…”

Section: Introductionmentioning

confidence: 99%

Novel CAG/CTG repeat expansion mutations do not contribute to the genetic risk for most cases of bipolar disorder or schizophrenia

Tsutsumi

Holmes

McInnis

et al. 2003

American J of Med Genetics Pt B

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The possible presence of anticipation in bipolar affective disorder and schizophrenia has led to the hypothesis that repeat expansion mutations could contribute to the genetic etiology of these diseases. Using the repeat expansion detection (RED) assay, we have systematically examined genomic DNA from 100 unrelated probands with schizophrenia and 68 unrelated probands with bipolar affective disorder for the presence of CAG/CTG repeat expansions. Our results show that 28% of the probands with schizophrenia and 30% of probands with bipolar disorder have a CAG/CTG repeat in the expanded range, but that each expansion could be explained by one of three nonpathogenic repeat expansions known to exist in the general population. We conclude that novel CAG/CTG repeat expansions are not a common genetic risk factor for bipolar disorder or schizophrenia.

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“…For example, GWAS and replication efforts support TCF4 as a risk locus for schizophrenia (Stefansson et al , 2009). However, a TCF4 CAG repeat was studied for association with schizophrenia in three studies (Bowen et al , 2000, McInnis et al , 2000, Vincent et al , 1999). All reported negative results which may have lead to the inappropriate exclusion of TCF4 from consideration.…”

Section: Discussionmentioning

confidence: 99%

Hypothesis-driven candidate genes for schizophrenia compared to genome-wide association results

Collins

Kim

Sklar³

et al. 2011

Psychol. Med.

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Background Candidate gene studies have been a key approach to the genetics of schizophrenia. Results of these studies have been confusing and no genes have been unequivocally implicated. The hypothesis-driven candidate gene literature can be appraised via comparison with the results of genome-wide association studies (GWAS). Methods We described the characteristics of hypothesis-driven candidate gene studies from SZGene, and used pathway analysis to compare hypothesis-driven candidate genes with GWAS results from the International Schizophrenia Consortium (ISC). Results SZGene contained 732 autosomal genes evaluated in 1,374 studies. These genes had poor statistical power to detect genetic effects typical for human diseases, assessed only 3.7% of genes in the genome, and had low marker densities per gene. Most genes were assessed once or twice (76.9%), providing minimal ability to evaluate consensus across studies. The ISC had power of 89% to detect a genetic effect typical for common human diseases and assessed 79% of known autosomal common genetic variation. Pathway analyses did not reveal enrichment of smaller ISC p-values in hypothesis-driven candidate genes nor did a comprehensive evaluation of meta-hypotheses driving candidate gene selection (schizophrenia as a disease of the synapse or neurodevelopment). The most studied hypothesis-driven candidate genes had no notable ISC results (COMT, DRD3, DRD2, HTR2A, NRG1, BDNF, DTNBP1, and SLC6A4). Conclusions We did not find support for the idea that the hypothesis-driven candidate genes studied in the literature were enriched for common variation involved in the etiology of schizophrenia. Larger samples are required definitively to evaluate this conclusion.

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Repeat sizes at CAG/CTG loci CTG18.1, ERDA1 and TGC13-7a in schizophrenia

Cited by 11 publications

References 0 publications

Early development and unstable genes in schizophrenia: preliminary results

Early development and unstable genes in schizophrenia: preliminary results

Novel CAG/CTG repeat expansion mutations do not contribute to the genetic risk for most cases of bipolar disorder or schizophrenia

Hypothesis-driven candidate genes for schizophrenia compared to genome-wide association results

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