title: Analysis of the hexanucleotide repeat expansion and founder haplotype at C9ORF72 in an Irish psychosis case-control sample.
abstract: The hexonucleotide repeat expansion 'GGGGCC' at the C9ORF72 gene has been strongly linked with amyotrophic lateral sclerosis and frontotemporal dementia. There is some evidence for clinical and genetic overlap between frontotemporal dementia and schizophrenia. Here, we genotyped the repeat at C9ORF72 in a large Irish psychosis case-control sample (n = 2477). We found no carriers of >30 repeats. We found 7 samples with >22 repeats, 2 schizophrenia cases and 5 controls, but overall we observed no difference in the distribution of the repeat between our case and control samples. By using genome-wide association data to phase haplotypes at this gene, we investigated if carriers of the repeat expansion arose from a single common founder. All samples that carry 17 or more repeats also carry the founder haplotype and overall there is a very strong correlation between repeat length and the founder haplotype (Spearman rho = 0.714, p < 0.001). Our study provides further evidence to bolster the claim that carriers of the repeat expansion at C9ORF72 arose from a single common founder.
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Ciara
authors.initials: C
authors.lastname: Fahey
authors.affiliation: Department of Neurology, Beaumont Hospital, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Byrne
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Russell
authors.initials: R
authors.lastname: McLaughlin
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kenna
authors.affiliation: Medical Research Council Centre for Neurodegeneration Research, King's College London, London, UK; Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Shatunov
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.affiliation: Medical Research Council Centre for Neurodegeneration Research, King's College London, London, UK; Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Chalabi
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bradley
authors.affiliation: Department of Neurology, Beaumont Hospital, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Aiden P
authors.initials: AP
authors.lastname: Corvin
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Electronic address: derek.morris@tcd.ie.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Morris
mesh_terms: D000073885:C9orf72 Protein; D016022:Case-Control Studies; D042622:DNA Repeat Expansion / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D011506:Proteins / Q000235:genetics*; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: Association; C9ORF72; Founder haplotype; Psychosis; Schizophrenia