A genomewide linkage study of age at onset in schizophrenia

Cardno, A. G., Holmans, Peter Andrew ORCID: https://orcid.org/0000-0003-0870-9412, Rees, M. I., Jones, L. A., McCarthy, G. M., Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931, Norton, N., Williams, H. J., Fenton, I., Murphy, K. C., Sanders, R. D., Gray, M. Y., O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, McGuffin, P. and Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 2011. A genomewide linkage study of age at onset in schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156B (8) , pp. 929-940. 10.1002/ajmg.1404

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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 genotyped 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	31 Oct 2022 09:21
URI:	https://orca.cardiff.ac.uk/id/eprint/80729

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