Evidence for a susceptibility locus for schizophrenia on chromosome 6pter–p22

Wang, Shengbiao; Sun, Cuie; Walczak, Cynthia A.; Ziegle, Janet; Kipps, Barbara R.; Goldin, Lynn R.; Diehl, Scott R.

doi:10.1038/ng0595-41

Cited by 231 publications

(135 citation statements)

References 31 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Large collections of pairs of affected relatives (usually sib pairs) have been studied for a number of complex illnesses, including non-insulin diabetes mellitus, 4,5 prostate cancer, 6 and schizophrenia. 7,8 Alternatively, small sets of large extended pedigrees have been used to study complex diseases such as early-onset Alzheimer's 9 and, most recently, Parkinson's disease. 10 Only a few large multiplex schizophrenia pedigrees are known to exist, 11 primarily because of exceptionally low rates of Correspondence: W Byerley, Department of Psychiatry, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, Utah 84132, USA.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

et al. 1998

View full text Add to dashboard Cite

A large multiplex schizophrenia pedigree ascertained from the Micronesian nation of Palau was genotyped with 406 microsatellite DNA markers evenly distributed throughout the genome. Assuming autosomal dominant inheritance, the highest genome-wide lod scores were found for DNA loci mapping to 2p13-14; the maximum lod score was 2.17 (theta = 0.05) at D2S441. A nonparametric APM analysis was also suggestive at D2S441 (APM score = 2.96, P = 0.011). Of the 14 affected cases in this extended family, eight share a large haplotype in this region spanning ෂ11 cM. When 16 other families containing 65 schizophrenic cases were typed in a follow-up study of this region, the maximum lod score remained positive (maximum at D2S441 1.69, theta = 0.20). APM results also remained positive at D2S441 for all 17 families (APM score = 4.87, P = 0.0006). The linkage and haplotype sharing results provide suggestive evidence for a 2p locus predisposing to schizophrenia in a subset of families in the Palauan population.

show abstract

Section: Introductionmentioning

confidence: 99%

Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

et al. 1998

View full text Add to dashboard Cite

show abstract

“…4 Further analysis in the entire set of 265 families revealed a maximum lod score of 3.51 with marker D6S296 in approximately 15-30% of the families. 13 Several other studies have also found evidence for linkage on the same fairly large chromosomal region.…”

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

View full text Add to dashboard Cite

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...

show abstract

“…More recently, loci involved in susceptibility to schizophrenia have also been described on chromosome 22 (Pulver et al, 1994a,b;Moises et al, 1995a;Schwab et al, 1995b andGill et al, 1996) and chromosome 6 (6p24-22) delimited by the markers D6S296, D6S285, D6S274, D6S260 and D6S259 (Straub et al, 1995;Schwab et al, 1995a, Moises et al, 1995bWang et al, 1995Wang et al, , 1996, as well as new additional regions on chromosomes 9 and 20 (Moises et al, 1995b) and 3 and 8 . In a study of linkage, using 15 markers covering 30 centimorgans of the 8p22-21 region of chromosome 8p, Kendler et al (1996) suggested that there might be a locus of vulnerability to schizophrenia on this chromosome.…”

Section: Reviewmentioning

confidence: 99%

“…Riley et al (1997) proposed a locus on chromosome 9 (9q34.3), corresponding to the gene for the N-methyl-D-aspartate receptor subunit. Consequently there is in the literature a tendency to admit a heterogeneity of loci (Moises et al, 1995b;Straub et al, 1995;Wang et al, 1995), with Risch (1990) suggesting a group of interacting loci in a "multilocus model". Citing many papers in support, Baron (1996) found "negative or ambiguous results" for a locus predisposing to schizophrenia on chromosome 6 (6p24-22) (Diehl et al, 1994;Mowry et al, 1995;Gurling et al, 1995;Antonarakis et al, 1995;Riley et al, 1995;Sasaki et al, 1995;Moises et al, 1995b), but more recent work (Wang et al, 1996) presents evidence of linkage disequilibrium between schizophrenia and the SCA 1 CAG repeat on chromosome 6p23 (SCA1 = gene for spinocerebellar ataxia type 1).…”

Section: Reviewmentioning

confidence: 99%

Localization of genes modulating the predisposition to schizophrenia: a revision

Lopes-Machado

Duarte

2000

Genet. Mol. Biol.

View full text Add to dashboard Cite

The genetics of schizophrenia or bipolar affective disorder has advanced greatly at the molecular level since the introduction of probes for the localization of specific genes. Research on gene candidates for susceptibility to schizophrenia can broadly be divided into two types, i.e., linkage studies, where a gene is found near a specific DNA marker on a specific chromosome, and association studies, when a condition is associated with a specific allele of a specific gene. This review covers a decade of publications in this area, from the 1988 works of Bassett et al. and Sherrington et al. on a gene localized on the long arm of chromosome 5 at the 5q11-13 loci, to the 1997 work of Lin et al. pointing to the 13q14.1-q32 loci of chromosome 13 and to the 1998 work of Wright et al. on an HLA DRB1 gene locus on chromosome 6 at 6p21-3. The most replicated loci were those in the long arm of chromosome 22 (22q12-q13.1) and on the short arm of chromosome 6 (6p24-22). In this critical review of the molecular genetic studies involved in the localization of genes which modulate the predisposition to schizophrenia the high variability in the results obtained by different workers suggests that multiple loci are involved in the predisposition to this illness.

show abstract

Evidence for a susceptibility locus for schizophrenia on chromosome 6pter–p22

Cited by 231 publications

References 31 publications

Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

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

Localization of genes modulating the predisposition to schizophrenia: a revision

Contact Info

Product

Resources

About