A genomewide linkage study of age at onset in schizophrenia

Alastair G. Cardno, Peter A. Holmans, Mark I. Rees, Lisa A. Jones, Geraldine M. McCarthy, Marian L. Hamshere, Nigel M. Williams, Nadine Norton, Hywel J. Williams, Iain Fenton, Kieran C. Murphy, Robert D. Sanders, Marion Y. Gray, Michael C. O'Donovan, Peter McGuffin, Michael J. Owen

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

There is strong evidence for a genetic contribution to age at onset of schizophrenia, which probably involves both susceptibility loci for schizophrenia and modifying loci acting independent of disease risk. We sought evidence of linkage to loci that influence age at onset of schizophrenia in a sample of 94 affected sibling pairs with DSM-IV schizophrenia or schizoaffective disorder, and age at first psychiatric contact of 45 years or less. Individuals were geno-typed for 229 microsatellite markers spaced at approximately 20 cM intervals throughout the genome. Loci contributing to age at onset were sought by a quantitative maximum-likelihood multipoint linkage analysis using MAPMAKER/SIBS. A nonparametric multipoint analysis was also performed. The genomewide significance of linkage results was assessed by simulation studies. There were six maximum-likelihood LOD score peaks of 1.5 or greater, the highest being on chromosome 17q (LOD = 2.54; genomewide P=0.27). This fulfils Lander and Kruglyak's [1995: Nat Genet 11:241-247] criteria for suggestive linkage in that it would be expected to occur once or less (0.3 times) per genome scan. However, this finding should be treated with caution because the LOD score appeared to be almost solely accounted for by the pattern of ibd sharing at one marker (D17S787), with virtually no evidence of linkage over flanking markers. None of the linkage results achieved genomewide statistical significance, but the LOD score peak on chromosome 13q (LOD=1.68) coincided with the region showing maximum evidence for linkage in the study by Blouin et al. [1998: Nat Genet 20:70-73] of categorical schizophrenia.

Original languageEnglish (US)
Pages (from-to)439-445
Number of pages7
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume105
Issue number5
DOIs
StatePublished - Jul 8 2001
Externally publishedYes

Fingerprint

Age of Onset
Schizophrenia
Viverridae
Chromosomes
Genome
Diagnostic and Statistical Manual of Mental Disorders
Psychotic Disorders
Microsatellite Repeats
Psychiatry

Keywords

  • Genetic
  • Genome
  • Linkage
  • Quantitative

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)
  • Genetics

Cite this

Cardno, A. G., Holmans, P. A., Rees, M. I., Jones, L. A., McCarthy, G. M., Hamshere, M. L., ... Owen, M. J. (2001). A genomewide linkage study of age at onset in schizophrenia. American Journal of Medical Genetics - Neuropsychiatric Genetics, 105(5), 439-445. https://doi.org/10.1002/ajmg.1404

A genomewide linkage study of age at onset in schizophrenia. / Cardno, Alastair G.; Holmans, Peter A.; Rees, Mark I.; Jones, Lisa A.; McCarthy, Geraldine M.; Hamshere, Marian L.; Williams, Nigel M.; Norton, Nadine; Williams, Hywel J.; Fenton, Iain; Murphy, Kieran C.; Sanders, Robert D.; Gray, Marion Y.; O'Donovan, Michael C.; McGuffin, Peter; Owen, Michael J.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 105, No. 5, 08.07.2001, p. 439-445.

Research output: Contribution to journalArticle

Cardno, AG, Holmans, PA, Rees, MI, Jones, LA, McCarthy, GM, Hamshere, ML, Williams, NM, Norton, N, Williams, HJ, Fenton, I, Murphy, KC, Sanders, RD, Gray, MY, O'Donovan, MC, McGuffin, P & Owen, MJ 2001, 'A genomewide linkage study of age at onset in schizophrenia', American Journal of Medical Genetics - Neuropsychiatric Genetics, vol. 105, no. 5, pp. 439-445. https://doi.org/10.1002/ajmg.1404
Cardno AG, Holmans PA, Rees MI, Jones LA, McCarthy GM, Hamshere ML et al. A genomewide linkage study of age at onset in schizophrenia. American Journal of Medical Genetics - Neuropsychiatric Genetics. 2001 Jul 8;105(5):439-445. https://doi.org/10.1002/ajmg.1404
Cardno, Alastair G. ; Holmans, Peter A. ; Rees, Mark I. ; Jones, Lisa A. ; McCarthy, Geraldine M. ; Hamshere, Marian L. ; Williams, Nigel M. ; Norton, Nadine ; Williams, Hywel J. ; Fenton, Iain ; Murphy, Kieran C. ; Sanders, Robert D. ; Gray, Marion Y. ; O'Donovan, Michael C. ; McGuffin, Peter ; Owen, Michael J. / A genomewide linkage study of age at onset in schizophrenia. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2001 ; Vol. 105, No. 5. pp. 439-445.
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