Association study of SNAP25 and schizophrenia in Irish family and case-control samples

A. H. Fanous, Z. Zhao, E. J.C.G. Van Den Oord, B. S. Maher, D. L. Thiselton, S. E. Bergen, B. Wormley, T. Bigdeli, R. L. Amdur, F. A. O'Neill, D. Walsh, K. S. Kendler, B. P. Riley

Research output: Contribution to journalArticlepeer-review

Abstract

SNAP25 occurs on chromosome 20p12.2, which has been linked to schizophrenia in some samples, and recently linked to latent classes of psychotic illness in our sample. SNAP25 is crucial to synaptic functioning, may be involved in axonal growth and dendritic sprouting, and its expression may be decreased in schizophrenia. We genotyped 18 haplotype-tagging SNPs in SNAP25 in a sample of 270 Irish high-density families. Single marker and haplotype analyses were performed in FBAT and PDT. We adjusted formultiple testing by computing q values. Association was followed up in an independent sample of 657 cases and 411 controls.We tested for allelic effects on the clinical phenotype by using the method of sequential addition and 5 factor-derived scores of the OPCRIT. Nine of 18 SNPs had Pvalues <0.05 in either FBAT or PDT for one or more definitions of illness. Several two marker haplotypes were also associated. Subjects inheriting the risk alleles of the most significantly associated two-marker haplotype were likely to have higher levels of hallucinations and delusions. The most significantly associated marker, rs6039820, was observed to perturb 12 transcription-factor binding sites in in silico analyses. An attempt to replicate association findings in the case - control sample resulted in no SNPs being significantly associated. We observed robust association in both single marker and haplotype-based analyses between SNAP25 and schizophrenia in an Irish family sample. Although we failed to replicate this in an independent sample, this gene should be further tested in other samples.

Original languageEnglish (US)
Pages (from-to)663-674
Number of pages12
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number2
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • Association
  • Clinical features
  • Polymorphism
  • SNAP25
  • Schizophrenia

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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