Genetic heterogeneity in schizophrenia: stratification of genome scan data using co-segregating related phenotypes

Pulver, A. E.; Mulle, J.; Nestadt, G.; Swartz, K. L.; Blouin, Jean-Louis; Dombroski, B.; Liang, K. Y.; Housman, D. E.; Kazazian, H. H.; Antonarakis, Stylianos; Lasseter, V. K.; Wolyniec, P. S.; Thornquist, M. H.; McGrath, J. A.

doi:10.1038/sj.mp.4000814

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Title		Genetic heterogeneity in schizophrenia: stratification of genome scan data using co-segregating related phenotypes
Authors		Pulver, A. E. Mulle, J. Nestadt, G. Swartz, K. L. Blouin, Jean-Louis Dombroski, B. Liang, K. Y. Housman, D. E. Kazazian, H. H. Antonarakis, Stylianos Lasseter, V. K. Wolyniec, P. S. Thornquist, M. H. McGrath, J. A. show all authors [1 - 14]
Published in		Molecular psychiatry. 2000, vol. 5, no. 6, p. 650-653
Abstract		Despite considerable effort to identify susceptibility loci for schizophrenia, none have been localized. Multiple genome scans and collaborative efforts have shown evidence for linkage to regions on chromosomes 1q, 5q, 6q, 8p, 13q, 10p and 22q.(1-9) Heterogeneity is likely. We previously mapped schizophrenia susceptibility loci (SSL) to chromosomes 13q32 (P = 0.00002) and 8p21-22 (P= 0.0001) using 54 multiplex pedigrees and suggested linkage heterogeneity. We have now stratified these families based on co-segregating phenotypes in non-schizophrenic first degree relatives (schizophrenia spectrum personality disorders (SSPD); psychotic affective disorders (PAD)). Genome scans were conducted for these phenotypic subgroups of families and broadened affected phenotypes were tested. The SSPD group provided its strongest genome-wide linkage support for the chromosome 8p21 region (D8S1771) using either narrow (non-parametric lod (NPL) P= 0.000002) or broadened phenotypes (NPL P = 0.0000008) and a new region of interest on 1p was identified (P = 0.006). For PAD families, the peak NPL in the genome scan occurred on chromosome 3p26-p24 (P = 0.008). The identification of multiple susceptibility loci for schizophrenia may be enhanced by stratification of families using psychiatric diagnoses of the non-schizophrenic relatives.
Keywords		Family Health — Genetic Heterogeneity — Genome, Human — Humans — Linkage (Genetics) — Phenotype — Schizophrenia/ genetics
Identifiers		DOI: 10.1038/sj.mp.4000814 PMID: 11126395
Full text		Article - Limited access to UNIGE Other version: http://www.nature.com/mp/journal/v5/n6/abs/4000814a.html
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Citation (ISO format)		PULVER, A. E. et al. Genetic heterogeneity in schizophrenia: stratification of genome scan data using co-segregating related phenotypes. In: Molecular psychiatry, 2000, vol. 5, n° 6, p. 650-653. doi: 10.1038/sj.mp.4000814 https://archive-ouverte.unige.ch/unige:8974