Psychiatry Research, 52: 135- 147 Elsevier 135 Pseudoautosomal Region in Schizophrenia: Linkage Analysis of Seven Loci by Sib-Pair and Lod-Score Methods Thierry d’Amato, Gilles Waksman, Maria Martinez, Claudine Laurent, Philip Gorwood, Dominique Campion, Maurice Jay, Christine Petit, Christine Savoye, Christian Bastard, Marie Claude Babron, FranCoise Clerget-Darpoux, and Jacques Mallet Received November 11, 1992; revised version received April 22, 1993; accepted September 13, 1993. Abstract. In a previous study, we reported a nonrandom segregation between schizophrenia and the pseudoautosomal locus DXYS14 in a sample of 33 sib- ships. That study has been extended by the addition of 16 new sibships from 16 different families. Data from six other loci of the pseudoautosomal region and of the immediately adjacent part of the X specific region have also been analyzed. Two methods of linkage analysis were used: the affected sibling pair (ASP) method and the lod-score method. Lod-score analyses were performed on the basis of three different models-A, B, and C-all shown to be consistent with the epidemiological data on schizophrenia. No clear evidence for linkage was obtained with any of these models. However, whatever the genetic model and the disease classification, maximum lod scores were positive with most of the markers, with the highest scores generally being obtained for the DXYS14 locus. When the ASP method was used, the earlier finding of nonrandom segregation between schizophrenia and the DXYS14 locus was still supported in this larger data set, at an increased level of statistical significance. Findings of ASP analyses were not significant for the other loci. Thus, findings obtained from analyses using the ASP method, but not the lod-score method, were consistent with the pseudoautosomal hypothesis for schizophrenia. Key Words. Genetics, chromosomes X and Y, linkage analysis, siblings. A significant body of evidence suggests that genetic factors play an important role in the pathogenesis of schizophrenia (for review, see Kendler, 1988). In recent years, most genetic studies in schizophrenia have focused on autosomal loci. For instance, loci from chromosome 5ql l-q13 have been extensively examined in linkage analyses. However, initially strong positive findings have not been replicated (for review, see Campion et al., 1992). Thierry d’Amato, M.D., is Chief, Clinique Assistant des Hopitaux, SHU de Psychiatric d’Adultes (Pr. Daltry), Hopital du Vinatier, Lyon-Bran. Dr. d’Amato and Gilles Waksman, Ph.D., are Research Scientists; Claudine Laurent, M.D., and Christine Savoye, M.D., are thesis students; and Jacques Mallet, Ph.D., is Chairman, Laboratoire de Gtnttique Moleculaire de la Neurotransmission et des Processus Neurodegtntratifs, CNRS, UMRC9923, Gif-sur-Yvette. Maria Martinez, Ph.D., Philip Gorwood, M.D., and Marie Claude Babron, Ph.D., are Research Scientists, and Francoise Clerget-Darpoux, Ph.D., is Director of Research, Laboratoire de Gtnttique Epidtmiologique, INSERM U-155, Chateau de Longchamp, Paris. Maurice Jay, M.D., is Chief of the Adult Psychiatry Service, Centre Hospitalier Specialis& de Saint Paul, Saint Paul, La Reunion. Christine Petit, Ph.D., is Director of Human Research, CNRS URA-1445, Institut Pasteur, Paris. Christian Bastard, Ph.D., is Chief, Service du Laboratoire de Cytogtnetique, CNTS, Bois Guillaume. (Reprint requests to Dr. T. d’Amato, Hopitat du Vinatier, 95 Boulevard Pinel, F-69677 Lyon-Bron, France.) 0165-1781/94/SO7.00 @ 1994 Elsevier Science Ireland Ltd.