Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q
Corresponding Author
Maria Martinez
Génétique des Maladies Humaines, Institut National de la Recherche et de la Santé Médicale, Paris, France
INSERM, U.358, Hôpital St-Louis, 1 Avenue Claude Vellefaux, 75 010 Paris, FranceSearch for more papers by this authorLynn R. Goldin
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorQuihe Cao
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorJing Zhang
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorAlan R. Sanders
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorDerek J. Nancarrow
Queensland Institute of Medical Research, Brisbane, Australia
Department of Psychiatry, University of Queensland, and Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Brisbane, Australia
Search for more papers by this authorJennifer M. Taylor
Queensland Institute of Medical Research, Brisbane, Australia
Search for more papers by this authorDouglas F. Levinson
Department of Psychiatry, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania
Search for more papers by this authorAndrew Kirby
Department of Psychiatry, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania
Search for more papers by this authorRaymond R. Crowe
Mental Health Clinical Research Center and Department of Psychiatry, The University of Iowa College of Medicine, Iowa City, Iowa
Search for more papers by this authorNancy C. Andreasen
Mental Health Clinical Research Center and Department of Psychiatry, The University of Iowa College of Medicine, Iowa City, Iowa
Search for more papers by this authorDonald W. Black
Mental Health Clinical Research Center and Department of Psychiatry, The University of Iowa College of Medicine, Iowa City, Iowa
Search for more papers by this authorJeremy M. Silverman
Department of Psychiatry, Mt. Sinai School of Medicine, New York, New York
Search for more papers by this authorDavid P. Lennon
Department of Psychiatry, University of Queensland, and Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Brisbane, Australia
Search for more papers by this authorDeborah A. Nertney
Department of Psychiatry, University of Queensland, and Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Brisbane, Australia
Search for more papers by this authorBryan J. Mowry
Department of Psychiatry, University of Queensland, and Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Brisbane, Australia
Search for more papers by this authorElliot S. Gershon
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorPablo V. Gejman
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorCorresponding Author
Maria Martinez
Génétique des Maladies Humaines, Institut National de la Recherche et de la Santé Médicale, Paris, France
INSERM, U.358, Hôpital St-Louis, 1 Avenue Claude Vellefaux, 75 010 Paris, FranceSearch for more papers by this authorLynn R. Goldin
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorQuihe Cao
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorJing Zhang
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorAlan R. Sanders
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorDerek J. Nancarrow
Queensland Institute of Medical Research, Brisbane, Australia
Department of Psychiatry, University of Queensland, and Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Brisbane, Australia
Search for more papers by this authorJennifer M. Taylor
Queensland Institute of Medical Research, Brisbane, Australia
Search for more papers by this authorDouglas F. Levinson
Department of Psychiatry, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania
Search for more papers by this authorAndrew Kirby
Department of Psychiatry, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania
Search for more papers by this authorRaymond R. Crowe
Mental Health Clinical Research Center and Department of Psychiatry, The University of Iowa College of Medicine, Iowa City, Iowa
Search for more papers by this authorNancy C. Andreasen
Mental Health Clinical Research Center and Department of Psychiatry, The University of Iowa College of Medicine, Iowa City, Iowa
Search for more papers by this authorDonald W. Black
Mental Health Clinical Research Center and Department of Psychiatry, The University of Iowa College of Medicine, Iowa City, Iowa
Search for more papers by this authorJeremy M. Silverman
Department of Psychiatry, Mt. Sinai School of Medicine, New York, New York
Search for more papers by this authorDavid P. Lennon
Department of Psychiatry, University of Queensland, and Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Brisbane, Australia
Search for more papers by this authorDeborah A. Nertney
Department of Psychiatry, University of Queensland, and Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Brisbane, Australia
Search for more papers by this authorBryan J. Mowry
Department of Psychiatry, University of Queensland, and Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Brisbane, Australia
Search for more papers by this authorElliot S. Gershon
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorPablo V. Gejman
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland
Search for more papers by this authorAbstract
Evidence for suggestive linkage to schizophrenia with chromosome 6q markers was previously reported from a two-stage approach. Using nonparametric affected sib pairs (ASP) methods, nominal p-values of 0.00018 and 0.00095 were obtained in the screening (81 ASPs; 63 independent) and the replication (109 ASPs; 87 independent) data sets, respectively. Here, we report a follow-up study of this 50cM 6q region using 12 microsatellite markers to test for linkage to schizophrenia. We increased the replication sample size by adding an independent sample of 43 multiplex pedigrees (66 ASPs; 54 independent). Pairwise and multipoint nonparametric linkage analyses conducted in this third data set showed evidence consistent with excess sharing in this 6q region, though the statistical level is weaker (p=0.013). When combining both replication data sets (total of 141 independent ASPs), an overall nominal p-value=0.000014 (LOD=3.82) was obtained. The sibling recurrence risk (λs) attributed to this putative 6q susceptibility locus is estimated to be 1.92. The linkage region could not be narrowed down since LOD score values greater than three were observed within a 13cM region. The length of this region was only slightly reduced (12cM) when using the total sample of independent ASPs (204) obtained from all three data sets. This suggests that very large sample sizes may be needed to narrow down this region by ASP linkage methods. Study of the etiological candidate genes in this region is ongoing. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:337–343, 1999. © 1999 Wiley-Liss, Inc.
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