Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder

L. E. DeLisi, S. Shaw, R. Sherrington, B. Nanthakumar, G. Shields, A. B. Smith, N. Wellman, V. W. Larach, J. Loftus, K. Razi, J. Stewart, M. Comazzi, A. Vita, M. De Hert, T. J. Crow

Resultado de la investigación: Article

35 Citas (Scopus)

Resumen

The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1.55 at the locus DXS8032 in Xq21. The present study with a new set of markers extended the cohort to 301 ill sibling pairs and their parents. Despite the increase in sample size, the LOD score did not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal Xp, a region remote from the previous report. Separating families into those who were more likely to have X chromosome inheritance (maternal with no male to male transmission) did not yield stronger findings. In spite of the evidence that psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is concluded that no consistent linkage of schizophrenia to the X chromosome can be demonstrated. In the context of the general failure of replication of linkage in psychosis, the possibility that the genetic predisposition to psychosis is contributed to by epigenetic modification rather than variations in the nucleotide sequence has to be considered. (C) 2000 Wiley-Liss, Inc.

Idioma originalEnglish
Páginas (desde-hasta)335-341
Número de páginas7
PublicaciónAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volumen96
N.º3
DOI
EstadoPublished - 12 jun 2000

Huella dactilar

X Chromosome
Psychotic Disorders
Schizophrenia
Sex Chromosomes
Siblings
Genetic Predisposition to Disease
Epigenomics
Sex Characteristics
Sample Size
Genes
Parents
Pathology
Brain
Population

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Citar esto

DeLisi, L. E. ; Shaw, S. ; Sherrington, R. ; Nanthakumar, B. ; Shields, G. ; Smith, A. B. ; Wellman, N. ; Larach, V. W. ; Loftus, J. ; Razi, K. ; Stewart, J. ; Comazzi, M. ; Vita, A. ; De Hert, M. ; Crow, T. J. / Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder. En: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2000 ; Vol. 96, N.º 3. pp. 335-341.
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abstract = "The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1.55 at the locus DXS8032 in Xq21. The present study with a new set of markers extended the cohort to 301 ill sibling pairs and their parents. Despite the increase in sample size, the LOD score did not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal Xp, a region remote from the previous report. Separating families into those who were more likely to have X chromosome inheritance (maternal with no male to male transmission) did not yield stronger findings. In spite of the evidence that psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is concluded that no consistent linkage of schizophrenia to the X chromosome can be demonstrated. In the context of the general failure of replication of linkage in psychosis, the possibility that the genetic predisposition to psychosis is contributed to by epigenetic modification rather than variations in the nucleotide sequence has to be considered. (C) 2000 Wiley-Liss, Inc.",
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DeLisi, LE, Shaw, S, Sherrington, R, Nanthakumar, B, Shields, G, Smith, AB, Wellman, N, Larach, VW, Loftus, J, Razi, K, Stewart, J, Comazzi, M, Vita, A, De Hert, M & Crow, TJ 2000, 'Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder', American Journal of Medical Genetics - Neuropsychiatric Genetics, vol. 96, n.º 3, pp. 335-341. https://doi.org/10.1002/1096-8628(20000612)96:3<335::AID-AJMG20>3.0.CO;2-E

Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder. / DeLisi, L. E.; Shaw, S.; Sherrington, R.; Nanthakumar, B.; Shields, G.; Smith, A. B.; Wellman, N.; Larach, V. W.; Loftus, J.; Razi, K.; Stewart, J.; Comazzi, M.; Vita, A.; De Hert, M.; Crow, T. J.

En: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 96, N.º 3, 12.06.2000, p. 335-341.

Resultado de la investigación: Article

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T1 - Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder

AU - DeLisi, L. E.

AU - Shaw, S.

AU - Sherrington, R.

AU - Nanthakumar, B.

AU - Shields, G.

AU - Smith, A. B.

AU - Wellman, N.

AU - Larach, V. W.

AU - Loftus, J.

AU - Razi, K.

AU - Stewart, J.

AU - Comazzi, M.

AU - Vita, A.

AU - De Hert, M.

AU - Crow, T. J.

PY - 2000/6/12

Y1 - 2000/6/12

N2 - The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1.55 at the locus DXS8032 in Xq21. The present study with a new set of markers extended the cohort to 301 ill sibling pairs and their parents. Despite the increase in sample size, the LOD score did not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal Xp, a region remote from the previous report. Separating families into those who were more likely to have X chromosome inheritance (maternal with no male to male transmission) did not yield stronger findings. In spite of the evidence that psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is concluded that no consistent linkage of schizophrenia to the X chromosome can be demonstrated. In the context of the general failure of replication of linkage in psychosis, the possibility that the genetic predisposition to psychosis is contributed to by epigenetic modification rather than variations in the nucleotide sequence has to be considered. (C) 2000 Wiley-Liss, Inc.

AB - The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1.55 at the locus DXS8032 in Xq21. The present study with a new set of markers extended the cohort to 301 ill sibling pairs and their parents. Despite the increase in sample size, the LOD score did not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal Xp, a region remote from the previous report. Separating families into those who were more likely to have X chromosome inheritance (maternal with no male to male transmission) did not yield stronger findings. In spite of the evidence that psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is concluded that no consistent linkage of schizophrenia to the X chromosome can be demonstrated. In the context of the general failure of replication of linkage in psychosis, the possibility that the genetic predisposition to psychosis is contributed to by epigenetic modification rather than variations in the nucleotide sequence has to be considered. (C) 2000 Wiley-Liss, Inc.

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