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, F. B. Lerer, D. Dikeos, R. R. Crowe, J. M. Silverman, D. F. Levinson, Anthony O'Neill

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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. Molecular Psychiatry (2009) 14, 786-795; doi:10.1038/mp.2009.11; published online 17 February 2009

Original languageEnglish
Pages (from-to)786-795
Number of pages10
JournalMolecular Psychiatry
Volume14
Issue number8
DOIs
Publication statusPublished - Aug 2009

Cite this

Holmans, P. A., Riley, B., Pulver, A. E., Owen, M. J., Wildenauer, D. B., Gejman, P. V., ... O'Neill, A. (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
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. ; Albus, M. ; Alexander, M. ; Godard, S. ; Ribble, R. ; Liang, K. Y. ; Norton, N. ; Maier, W. ; Papadimitriou, G. ; Walsh, D. ; Jay, M. ; Lerer, F. B. ; Dikeos, D. ; Crowe, R. R. ; Silverman, J. M. ; Levinson, D. F. ; O'Neill, Anthony. / Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms. In: Molecular Psychiatry. 2009 ; Vol. 14, No. 8. pp. 786-795.
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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. Molecular Psychiatry (2009) 14, 786-795; doi:10.1038/mp.2009.11; published online 17 February 2009",
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Holmans, PA, Riley, B, Pulver, AE, Owen, MJ, Wildenauer, DB, Gejman, PV, Mowry, BJ, Laurent, C, Kendler, KS, Nestadt, G, Williams, NM, Schwab, SG, Sanders, AR, Nertney, D, Mallet, J, Wormley, B, Lasseter, VK, O'Donovan, MC, Duan, J, Albus, M, Alexander, M, Godard, S, Ribble, R, Liang, KY, Norton, N, Maier, W, Papadimitriou, G, Walsh, D, Jay, M, Lerer, FB, Dikeos, D, Crowe, RR, Silverman, JM, Levinson, DF & O'Neill, A 2009, 'Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms', Molecular Psychiatry, vol. 14, no. 8, pp. 786-795. https://doi.org/10.1038/mp.2009.11

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms. / 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.; Albus, M.; Alexander, M.; Godard, S.; Ribble, R.; Liang, K. Y.; Norton, N.; Maier, W.; Papadimitriou, G.; Walsh, D.; Jay, M.; Lerer, F. B.; Dikeos, D.; Crowe, R. R.; Silverman, J. M.; Levinson, D. F.; O'Neill, Anthony.

In: Molecular Psychiatry, Vol. 14, No. 8, 08.2009, p. 786-795.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms

AU - Holmans, P. A.

AU - Riley, B.

AU - Pulver, A. E.

AU - Owen, M. J.

AU - Wildenauer, D. B.

AU - Gejman, P. V.

AU - Mowry, B. J.

AU - Laurent, C.

AU - Kendler, K. S.

AU - Nestadt, G.

AU - Williams, N. M.

AU - Schwab, S. G.

AU - Sanders, A. R.

AU - Nertney, D.

AU - Mallet, J.

AU - Wormley, B.

AU - Lasseter, V. K.

AU - O'Donovan, M. C.

AU - Duan, J.

AU - Albus, M.

AU - Alexander, M.

AU - Godard, S.

AU - Ribble, R.

AU - Liang, K. Y.

AU - Norton, N.

AU - Maier, W.

AU - Papadimitriou, G.

AU - Walsh, D.

AU - Jay, M.

AU - Lerer, F. B.

AU - Dikeos, D.

AU - Crowe, R. R.

AU - Silverman, J. M.

AU - Levinson, D. F.

AU - O'Neill, Anthony

PY - 2009/8

Y1 - 2009/8

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AB - 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. Molecular Psychiatry (2009) 14, 786-795; doi:10.1038/mp.2009.11; published online 17 February 2009

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