No Evidence for a Pseudoautosomal Locus for Schizophrenia

Asherson, Philip; Parfitt, E.; Sargeant, M.; Tidmarsh, S. F.; Buckland, Paul Robert; Taylor, Colin; Clements, Alison; Gill, M.; McGuffin, Peter; Owen, Michael John

doi:10.1192/bjp.161.1.63

Cited by 47 publications

(17 citation statements)

References 23 publications

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“…In particular, a number of reports investigated the possibility that such a locus exists within the pseudoautosomal region of the X‐chromosome. The results of these studies, however, are conflicting (d'Amato et al, 1992; d'Amato et al, 1994; Asherson et al, 1992; Laval et al, 1998; Maier et al, 1995; Okoro et al, 1995; Wang et al, 1993). Nonpseudoautosomal regions of the X‐chromosome also have been implicated in the pathogenesis of schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Turner syndrome in schizophrenia

2000

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Both Turner syndrome and schizophrenia are relatively infrequent conditions. Consequently, individuals having both illnesses are rare. Previous reviews of sex chromosome abnormalities in schizophrenia have focused primarily on the presence of supernumerary X-chromosomes. After identifying two female patients with schizophrenia and Turner syndrome, we reevaluated the available literature that survey female schizophrenics for the presence of chromosomal abnormalities. Eleven patients with Turner syndrome were identified among 6,483 females with schizophrenia in non-case-report studies. These survey results indicate that Turner syndrome occurs approximately three-fold more frequently in schizophrenic females than in the general female population (P < 0.02). Including 6 other case reports and our 2 cases, a total of 19 females with both schizophrenia and Turner syndrome were reported. Interestingly, whereas most Turner syndrome patients have the 45,X karyotype, the majority (18/19) of women with both illnesses have a mosaic karyotype (P < 0.0002). Given the potential role of genes on the X-chromosome in the pathogenesis of schizophrenia, the study of unique populations with abnormalities in this chromosome, such as women with Turner syndrome, may offer clues into this illness.

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Section: Discussionmentioning

confidence: 99%

Investigation of Turner syndrome in schizophrenia

2000

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“…across locations and studies [Asherson et al, 1992;Wang et al, 1993;Barr et al, 1994;Crow et al, 1994]. An unusual case of an XX male with schizophrenia [Nanko, 1981] was found to have one breakpoint within PAR1 and the second within the Yp11.2 homologous region [Ross et al, 2001]; the significance remains unclear.…”

Section: Formulations Of the Hypothesismentioning

confidence: 99%

The XY gene hypothesis of psychosis: Origins and current status

Crow

2013

American J of Med Genetics Pt B

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Sex differences in psychosis and their interaction with laterality (systematic departures from 50:50 left-right symmetry across the antero-posterior neural axis) are reviewed in the context of the X-Y gene hypothesis. Aspects of laterality (handedness/cerebral asymmetry/the torque) predict (1) verbal and non-verbal ability in childhood and across adult life and (2) anatomical, physiological, and linguistic variation relating to psychosis. Neuropsychological and MRI evidence from individuals with sex chromosome aneuploidies indicates that laterality is associated with an X-Y homologous gene pair. Within each mammalian species the complement of such X-Y gene pairs reflects their potential to account for taxon-specific sexual dimorphisms. As a consequence of the mechanism of meiotic suppression of unpaired chromosomes such X-Y gene pairs generate epigenetic variation around a species defining motif that is carried to the zygote with potential to initiate embryonic gene expression in XX or XY format. The Protocadherin11XY (PCDH11XY) gene pair in Xq21.3/Yp11.2 in probable coordination with a gene or genes within PAR2 (the second pseudo-autosomal region) is the prime candidate in relation to cerebral asymmetry and psychosis in Homo sapiens. The lately-described pattern of sequence variation associated with psychosis on the autosomes may reflect a component of the human genome's adjustment to selective pressures generated by the sexually dimorphic mate recognition system. © 2013 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by John Wiley and Sons, Ltd.

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“…IDDM exhibits 30-50% concordance in monozygotic twins, and an average risk to sibs of 6% [Pearson, 1994;Todd, 19901, heritability similar to the risks seen in schizophrenia. Recently, exclusions of certain regions of the genome for schizophrenia [Wang et al, 1993a,b;Su et al, 1993;Hallmeyer et al, 19921 or failures to support linkage DeLisi et al, 1994;Coon et al, 1994;Barr et al, 1994; Aschauer et al, 1990;Asherson et al, 1992Asherson et al, , 1993Gill et al, 19931 have been reported. Given methodological issues and the probable etiologic heterogeneity, no one region of the genome can be excluded for potential importance to the susceptibility to schizophrenia in some families.…”

Section: Introductionmentioning

confidence: 99%

Schizophrenia: A genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes

et al. 1995

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Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have carried out linkage studies of 520 loci, covering approximately 70% of the genome for susceptibility loci for schizophrenia. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration. In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed using dominant, recessive, and "affected only" models and nonparametric sib pair identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses gave a P value = .0001, corresponding to a lod score approximately equal to 3.00. For 8p22-p21, the maximum two-point lod score occurred using the "affected only" recessive model (ZMAX = 2.35; theta M = theta F); allowing for a constant sex difference in recombination fractions found in reference pedigrees, ZMAX = 2.78 (theta M/theta F = 3). For a second region, 3p26-p24, the maximum two-point lod score was 2.34 ("affected only" dominant model), and the affected sib-pair P value was .01. These two regions are worthy of further exploration as potential sites of susceptibility genes for schizophrenia.

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No Evidence for a Pseudoautosomal Locus for Schizophrenia

Cited by 47 publications

References 23 publications

Investigation of Turner syndrome in schizophrenia

Investigation of Turner syndrome in schizophrenia

The XY gene hypothesis of psychosis: Origins and current status

Schizophrenia: A genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes

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