Schizophrenia susceptibility and chromosome 6p24–22

Mowry, Bryan; Nancarrow, Derek J.; Lennon, David P.; Sandkuijl, Lodewijk A.; Crowe, Raymond R.; Silverman, Jeremy M.; Mohs, Richard C.; Siever, Larry J.; Endicott, Jean; Sharpe, Lawrence; Walters, Marilyn K.; Hayward, Nicholas K.; Levinson, Douglas F.

doi:10.1038/ng1195-233

Cited by 68 publications

(43 citation statements)

References 8 publications

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“…Findings consistent with this work have subsequently been reported [15,23], although not consistently [1,9,16]. A multicenter study examined the 6p linkage and also a locus in chromosome 8 [22].…”

supporting

confidence: 75%

Recent Advances in Genetic Research on Schizophrenia

Tsuang

1998

J Biomed Sci

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supporting

confidence: 75%

Recent Advances in Genetic Research on Schizophrenia

Tsuang

1998

J Biomed Sci

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“…Other replication attempts failed. [35][36][37][38][39] A collaborative multicenter study, which included most of the samples of schizophrenia families held around the world, found increased allele sharing of 55.9% and a multipoint maximum likelihood score (MLS) of 2.19 (P ¼ 0.001) excluding the ISHDSF and 2.68 (P ¼ 0.0004) including the ISHDSF families. 40 Two meta-analyses provided strong support for linkage to several markers in the 6p region, 41,42 one did not.…”

Section: Introductionmentioning

confidence: 99%

Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families.

et al. 2003

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A recent report showed significant associations between several SNPs in a previously unknown EST cluster with schizophrenia. 1 The cluster was identified as the human dystrobrevin binding protein 1 gene (DTNBP1) by sequence database comparisons and homology with mouse DTNBP1. 2 However, the linkage disequilibrium (LD) among the SNPs in DTNBP1 as well as the pattern of significant SNP-schizophrenia association was complex. This raised several questions such as the number of susceptibility alleles that may be involved and the size of the region where the actual disease mutation(s) could be located. To address these questions, we performed different single-marker tests on the 12 previously studied and 2 new SNPs in DTNBP1 that were re-scored using an improved procedure, and performed a variety of haplotype analyses. The sample consisted of 268 Irish multiplex families selected for high density of schizophrenia. Results suggested a simple structure where the LD in the target region could be explained by 6 haplotypes that together accounted for 96% of haplotype diversity in the whole sample. From these six, a single high-risk haplotype was identified that showed a significant association with schizophrenia and explained the pattern of significant findings in the analyses with individual markers. This haplotype was 30 kb long, had a large effect, could be measured with two tag SNPs only, had a frequency of 6% in our sample, seemed to be of relatively recent origin in evolutionary terms, and was equally distributed over Ireland. Implications of these findings for follow-up and replication studies are discussed.

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“…5,14,15 However, several other groups have not been able to confirm the results. [16][17][18] A large multicenter study including some of the above mentioned datasets found some evidence for linkage with a maximum lod score of 2.19. 12 Interestingly, Brzustowicz et al 19 found evidence for linkage in Canadian families on the same region when they used a quantitative trait measure for positive-symptom scores suggesting that the schizophrenia susceptibility locus on this region may be related to the severity of psychotic symptoms.…”

mentioning

confidence: 99%

Linkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set

et al. 1998

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During the past decade numerous studies have been published describing chromosomal regions potentially linked with schizophrenia. Unfortunately, none of these studies has been able to conclusively identify any specific gene that predisposes to schizophrenia. Typically evidence for linkage is seen on large chromosomal regions, as expected, containing tens or even hundreds of genes. Furthermore, attempts to replicate the findings have rarely been successful leaving a confusion about the existence of predisposing genes for schizophrenia in a particular region of the genome. We have carried out linkage analysis in a set of 62 pedigrees rising from a genetically isolated population of Finland with markers on six chromosomal regions earlier suggested to harbor predisposing genes for schizophrenia, namely 3p, 1 5q, 2,3 6p, 4 8p, 1 20p, 5 and 22q. 6,7 We were not able to find significant evidence for linkage on any of these chromosomal regions. However, some support for linkage was found on all studied chromosomal regions, except 3p.We identified all Finnish patients with schizophrenia born between 1940 and 1969 (n = 29 124). 8 Patients who had received disability pension or free medication because of schizophrenia were identified from two registers of the Social Insurance Institution, and patients who had been hospitalized for schizophrenia were identified from the National Hospital Discharge Register. All three registers were computerized in 1968; ICD-8 diagnostic criteria and codes were used before 1987, since when psychiatric diagnoses have been coded according to ICD-9 applying DSM-III-R diagnostic criteria. We accepted all probands with a 295 diagnosis according to the ICD-8 and ICD-9 numbering scheme; this includes patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder. Parents and siblings were identified from the National Population Register, and information on these relatives was linked to the health care registers to obtain data on their hospital treatments, pensions, and free medications.From these pedigrees, families with at least three affected family members were identified (n = 312), and those with at least one unaffected and three affected children were asked to participate in the study. If both parents were affected, the family was excluded. Diagnoses were confirmed as described in methods. Some families refused to participate and some were excluded because of uncertain diagnoses, and finally 62 families were used for molecular genetic studies out of 102 families who were asked to participate. Three different diagnostic classes were constructed as follows: class 1 contained 137 cases of DSM-IV schizophrenia, class 2 added 23 cases with schizoaffective disorder, and class 3 another 29 individuals with schizophrenia spectrum conditions (schizophreniform disorder, schizotypal personality disorder, schizoid personality disorder, delusional disorder, brief psychotic disorder, and psychotic disorder NOS). Patients with bipolar disorder or major depressive disorder were classifie...

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Schizophrenia susceptibility and chromosome 6p24–22

Cited by 68 publications

References 8 publications

Recent Advances in Genetic Research on Schizophrenia

Recent Advances in Genetic Research on Schizophrenia

Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families.

Linkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set

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