Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence is presented for the occurrence of a locus for schizotaxia on the short arm of chromosome 6. This derives from study of 63 informative members of seven pedigrees in which the proband and a parent (or a sib of parent) suffered with schizophrenia and other kin were either normal or fell within a spectrum of conditions related to schizophrenia. For linkage of HLA and schizotaxia a Lod score, 2.57, at recombination frequency 0.15 is reported, which gives p = 0.008. This is in contrast to data on 54 informative members of six pedigrees with atypical (schizo-affective or mixed) psychoses in two generations. Glyoxalase isoenzymes were of value in linkage analysis in two pedigrees. No evidence for linkage was found for any erythrocyte surface antigen nor for 15 other genetic markers. Details for each pedigree are provided.
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PMID:Genetic markers for schizotaxia. 42 Sep

We tested the hypothesis of linkage of HLA (human leukocyte antigens) and schizophrenia in 10 nuclear families that were ascertained on the basis of at least two siblings affected with chronic schizophrenia (SCH), as defined by Research Diagnostic Criteria, with or without superimposed affective disorder. All available parents and siblings were interviewed and typed for HLA antigens at the A, B, C, and Dr loci. Lod scores for linkage between HLA and a putative SCH-locus were calculated using the program LIPED, assuming several possible models for the mode of transmission of the SCH locus. Linkage was also tested with DSM-III schizotypal and paranoid personality disorders considered as part of the illness phenotype. The lod score analysis indicated that for most models of inheritance of schizophrenia, close linkage to HLA could be excluded. The results did not change if individuals with "spectrum" disorders were considered affected. We also tested for linkage using the affected sib-pair method which does not require any assumptions about the mode of transmission of the illness. The results of this analysis also indicated that linkage to HLA was very unlikely. If our results are considered together with other published studies, a susceptibility locus for schizophrenia or "schizophrenia spectrum" is not likely to be in the HLA region of chromosome 6.
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PMID:Relationship of HLA to schizophrenia in 10 nuclear families. 356 92

Previous results of a genome-wide survey for schizophrenia susceptibility genes in nine multiplex families indicated a possible region of linkage on chromosome 22. We therefore tested for linkage using ten highly polymorphic chromosome 22 DNA markers. Lod score analyses were suggestive of linkage for several markers on the distal end of the chromosome; however, no lod score exceeded 3 assuming either autosomal dominant or autosomal recessive transmission. The highest lod score was 2.09 (theta = 0.10) for marker D22S276 under autosomal recessive inheritance. Based on simulation analyses, this result is unlikely to represent a false positive. Analyses using information from affected individuals only resulted in reduced lod scores, with a maximum of 1.40 (theta = 0.05) for D22S276 assuming autosomal recessive inheritance. Two nonparametric methods, sib pair analysis and the Affected-Pedigree-Member method, also yielded suggestive but inconclusive findings; results were positive, but strict thresholds of significance were not met. Additionally, we tested one candidate gene, the Arylsulfatase A gene, located in the region of 22q13.31-qter. Results were again inconclusive, though the DNA marker available for this gene was a 2-allele RFLP with heterozygosity of 0.5, and therefore not maximally informative. Further investigation of this chromosomal region and this and other candidate genes may be warranted.
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PMID:Analysis of chromosome 22 markers in nine schizophrenia pedigrees. 790 93

In a previous study, we reported a nonrandom segregation between schizophrenia and the pseudoautosomal locus DXYS14 in a sample of 33 sibships. That study has been extended by the addition of 16 new sibships from 16 different families. Data from six other loci of the pseudoautosomal region and of the immediately adjacent part of the X specific region have also been analyzed. Two methods of linkage analysis were used: the affected sibling pair (ASP) method and the lod-score method. Lod-score analyses were performed on the basis of three different models--A, B, and C--all shown to be consistent with the epidemiological data on schizophrenia. No clear evidence for linkage was obtained with any of these models. However, whatever the genetic model and the disease classification, maximum lod scores were positive with most of the markers, with the highest scores generally being obtained for the DXYS14 locus. When the ASP method was used, the earlier finding of nonrandom segregation between schizophrenia and the DXYS14 locus was still supported in this larger data set, at an increased level of statistical significance. Findings of ASP analyses were not significant for the other loci. Thus, findings obtained from analyses using the ASP method, but not the lod-score method, were consistent with the pseudoautosomal hypothesis for schizophrenia.
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PMID:Pseudoautosomal region in schizophrenia: linkage analysis of seven loci by sib-pair and lod-score methods. 797 70

Markers for X chromosome loci were used in linkage studies of a large group of small families (n = 126) with at least two schizophrenic members in one sibship. Based on the hypothesis that a gene for schizophrenia could be X-Y linked, with homologous loci on both X and Y, our analyses included all families regardless of the pattern of familial inheritance. Lod scores were computed with both standard X-linked and a novel X-Y model, and sib-pair analyses were performed for all markers examining the sharing of maternal alleles. Small positive lod scores were obtained for loci pericentromeric, from Xp11.4 to Xq12. Lod scores were also computed separately in families selected for evidence of maternal inheritance and absence of male to male transmission of psychosis. The lod score for linkage to the locus DXS7 reached a maximum of 1.83 at 0.08% recombination, assuming dominant inheritance on the X chromosome in these families (n = 34). Further investigation of the X-Y homologous gene hypothesis focussing on this region is warranted.
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PMID:Search for linkage to schizophrenia on the X and Y chromosomes. 807 61

A pseudoautosomal locus for schizophrenia has been proposed based on observations of an excess of same-sex affected sibling pairs over opposite-sex pairs when the transmitting parent is the father. Such a pattern of partial concordance by sex related to paternal transmission would be difficult to explain by any biologic mechanism other than pseudoautosomal transmission of schizophrenia. To test the pseudoautosomal hypothesis, 37 sibling pairs concordant for the schizophrenia spectrum were identified from 24 nuclear pedigrees. No significant difference in concordance for sex was found between sibships of paternal and maternal transmission of schizophrenia. Next, a linkage analysis was performed in 12 informative pedigrees, examining seven marker loci spanning the pseudoautosomal region. Both strict schizophrenia and a broader schizophrenia spectrum were analyzed as the affected phenotype, and both autosomal dominant and autosomal recessive models were tested. None of the markers supported linkage to either schizophrenia or the schizophrenia spectrum. Lod scores of less than -4 were obtained across the entire pseudoautosomal region by means of multipoint linkage analyses in the autosomal dominant model. In the autosomal recessive model, the respective lod scores were less than -2. We conclude that there is no evidence of a pseudoautosomal locus for schizophrenia in our pedigrees in any of the genetic models we tested.
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PMID:Pseudoautosomal locus for schizophrenia excluded in 12 pedigrees. 843 40

Pulver et al. [1994a] reported modest linkage evidence for a dominantly (D) inherited "schizophrenia gene" in the vicinity of IL2RB on chromosome 22q12, and Coon et al. [1994] adduced moderate evidence under a recessive (R) model. We report here a replication study to test the hypothesis that one of these two models (or a third, intermediate (I) model) adequately describes the co-segregation of schizophrenia and chromosome 22q12 markers in an independent sample of 23 multiplex families. Altogether nine transmission models were evaluated. The models differed depending on whether the 15 family members with a diagnosis of schizophrenia spectrum disorders were considered unaffected (a "narrow" (N) definition), affected (a "wide" (W) definition), or declared "unknown" (U). The entire region between D22S268 and D22S307 is excluded (i.e., lod <-2) for models RN, RW, RU, and IW. Lod scores for the remaining models are uniformly negative; albeit, equivocal with respect to the dominant hypothesis over a small region between D22S268 and IL2RB. Nonparametric analysis under both diagnostic criteria also failed to yield any evidence for a susceptibility locus in this region of chromosome 22.
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PMID:No evidence for a schizophrenia susceptibility gene in the vicinity of IL2RB on chromosome 22. 925 69

Eight Utah multigenerational families, each with three to six cases of schizophrenia, were phenotyped with two specific measures of inhibitory neurophysiological functioning, P50 auditory sensory gating (P50), and antisaccade ocular motor performance (AS). A genomewide linkage analysis was performed to screen for loci underlying a qualitative phenotype combining the P50 and AS measures. For this composite inhibitory phenotype, the strongest evidence for linkage was to the D22s315 marker on chromosome 22q (lod score = 3.55, theta = 0) under an autosomal dominant model. Simulation analyses indicate that this 3.55 lod score is unlikely to represent a false positive result. Lod scores were 2.0 or greater for markers flanking D22s315. A nonparametric linkage (NPL) analysis of the chromosome 22 data showed evidence for allele sharing over the broad region surrounding D22s315 with a maximum NPL score of 3.83 (p = .002) for all pedigrees combined.
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PMID:Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families. 1049 Jul 14

The vitamin D hypothesis of schizophrenia is a recent concept bringing together old observations on environmental risk factors and new findings on the neurodevelopmental effects of vitamin D. Candidate genes related to the vitamin D endocrine system have not yet been fully explored for this purpose. The coexistence of vitamin-D-dependent-rickets type II with alopecia (VDDR IIA) and different forms of psychosis in the same inbred family has provided us with an opportunity to investigate the presumed relationship between vitamin D deficiency and psychosis. Psychiatric examination and molecular genetic studies were performed in this family overloaded with psychotic disorders and VDDR IIA. Forty members were evaluated in order to describe their phenotypic features. The family was tested for a linkage to the chromosome 12q12-q14 region where the vitamin D receptor (VDR) gene is located. Psychosis was the common phenotype in the 18 psychiatrically affected members. Pedigree analysis did not show a cosegregation of psychosis and rickets. Lod scores were not significant to prove a linkage between psychosis and VDR locus. The authors concluded that (1) the neurodevelopmental consequences of vitamin D deficiency do not play a causative role in psychotic disorders, (2) these two syndromes are inherited independently, and (3) vitamin D deficiency does not act as a risk factor in subjects susceptible to psychosis.
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PMID:Is vitamin D hypothesis for schizophrenia valid? Independent segregation of psychosis in a family with vitamin-D-dependent rickets type IIA. 1475 20