Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms

P. A. Holmans, B. Riley, A. E. Pulver, M. J. Owen, D. B. Wildenauer, P. V. Gejman, B. J. Mowry, C. Laurent, K. S. Kendler, G. Nestadt, N. M. Williams, S. G. Schwab, A. R. Sanders, D. Nertney, J. Mallet, B. Wormley, V. K. Lasseter, M. C. O'Donovan, J. Duan, M. AlbusM. Alexander, S. Godard, R. Ribble, K. Y. Liang, N. Norton, W. Maier, G. Papadimitriou, D. Walsh, M. Jay, A. O'Neill, F. B. Lerer, D. Dikeos, R. R. Crowe, J. M. Silverman, D. F. Levinson

Research output: Contribution to journalArticle

Abstract

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage (European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region.

Original languageEnglish (US)
Pages (from-to)786-795
Number of pages10
JournalMolecular psychiatry
Volume14
Issue number8
DOIs
StatePublished - Aug 2009

Keywords

  • Genetic predisposition to disease
  • Genetics
  • Genome
  • Genotype
  • Human
  • Humans
  • Linkage (genetics)
  • Schizophrenia/

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Holmans, P. A., Riley, B., Pulver, A. E., Owen, M. J., Wildenauer, D. B., Gejman, P. V., Mowry, B. J., Laurent, C., Kendler, K. S., Nestadt, G., Williams, N. M., Schwab, S. G., Sanders, A. R., Nertney, D., Mallet, J., Wormley, B., Lasseter, V. K., O'Donovan, M. C., Duan, J., ... Levinson, D. F. (2009). Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms. Molecular psychiatry, 14(8), 786-795. https://doi.org/10.1038/mp.2009.11