Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study

Dieter B. Wildenauer, Sibylle G. Schwab, Margot Albus, Joachim Hallmayer, Bernard Lerer, Wolfgang Maier, Douglas Blackwood, Walter Muir, David St Clair, Stewart Morris, Hans W. Moises, Liu Yang, Helgi Kristbjarnarson, Tomas Helgason, Claudia Wiese, David A. Collier, Peter Holmans, Jo Daniels, Mark Rees, Philip AshersonQueta Roberts, Alastair Cardno, Maria J. Arranz, Homero Vallada, David Ball, Hiroshi Kunugi, Robin M. Murray, John F. Powell, Sin Nanko, Pak Sham, Mike Gill, Peter McGuffin, Michael J. Owen, Ann E. Pulver, Stylianos E. Antonarakis, Robert Babb, Jean Louis Blouin, Nicola DeMarchi, Beth Dombroski, David Housman, Maria Karayiorgou, Jurg Ott, Laura Kasch, Haig Kazazian, Virginia K. Lasseter, Erika Loetscher, Hermann Luebbert, Gerald Nestadt, Carl Ton, Paula S. Wolyniec, Claudine Laurent, Michel de Chaldee, Florence Thibaut, Maurice Jay, Daniele Samolyk, Michel Petit, Dominique Campion, Jacques Mallet, Richard E. Straub, Charles J. MacLean, Stephen M. Easter, F. Anthony O'Neill, Dermot Walsh, Kenneth S. Kendler, Pablo V. Gejman, Qiuhe Cao, Elliot Gershon, Judith Badner, Ethiopia Beshah, Jing Zhang, Brien P. Riley, Swarnageetha Rajagopalan, Mpala Mogudi-Carter, Trefor Jenkins, Robert Williamson, Lynn E. DeLisi, Chad Garner, Mary Kelly, Carrie LeDuc, Lon Cardon, Jay Lichter, Tim Harris, Josephine Loftus, Gail Shields, Margarite Comasi, Antonio Vita, Angela Smith, Jay Dann, Geoff Joslyn, Hugh Gurling, Gursharan Kalsi, Jon Brynjolfsson, David Curtis, Thordur Sigmundsson, Robert Butler, Tim Read, Patrice Murphy, Andrew Chih Hui Chen, Hannes Petursson, Bill Byerley, Mark Hoff, John Holik, Hilary Coon, Douglas F. Levinson*, Derek J. Nancarrow, Raymond R. Crowe, Nancy Andreasen, Jeremy M. Silverman, Richard C. Mohs, Larry J. Siever, Jean Endicott, Lawrence Sharpe, Marilyn K. Walters, David P. Lennon, Nicholas K. Hayward, Lodewijk A. Sandkuijl, Bryan J. Mowry, Harald N. Aschauer, Kurt Meszaros, Elisabeth Lenzinger, Karoline Fuchs, Liu Yang, Angela M. Heiden, Hans W. Moises, Leonid Kruglyak, Mark J. Daly, Tara C. Matise

*Corresponding author for this work

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = .001) and 2.68 (Combined sample, p=.0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p=.0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.

Original languageEnglish
Pages (from-to)580-594
Number of pages15
JournalAmerican Journal of Medical Genetics
Volume67
Issue number6
Publication statusPublished - 1996

Keywords

  • Collaboration
  • Genetic linkage
  • Genotype levinson
  • Polymorphism
  • Schizophrenia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Wildenauer, D. B., Schwab, S. G., Albus, M., Hallmayer, J., Lerer, B., Maier, W., Blackwood, D., Muir, W., St Clair, D., Morris, S., Moises, H. W., Yang, L., Kristbjarnarson, H., Helgason, T., Wiese, C., Collier, D. A., Holmans, P., Daniels, J., Rees, M., ... Matise, T. C. (1996). Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study. American Journal of Medical Genetics, 67(6), 580-594.