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• W2094507913 abstract "<h3>Context</h3> Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity. <h3>Objective</h3> To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes. <h3>Design</h3> Latent class and linkage analysis. <h3>Setting</h3> Taiwanese field research centers. <h3>Participants</h3> The latent class analysis included 1236 Han Chinese individuals with<i>DSM-IV</i>schizophrenia. These individuals were members of a large affected-sibling-pair sample of schizophrenia (606 ascertained families), original linkage analyses of which detected a maximum logarithm of odds (LOD) of 1.8 (<i>z</i> = 2.88) on chromosome 10q22.3. <h3>Main Outcome Measures</h3> Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores. <h3>Results</h3> Latent class analyses identified 4 classes, with 2 demonstrating familial aggregation. The first (LC2) described a group with severe negative symptoms, disorganization, and pronounced functional impairment, resembling “deficit schizophrenia.” The second (LC3) described a group with minimal functional impairment, mild or absent negative symptoms, and low disorganization. Using the negative/deficit subtype, we detected genome-wide significant linkage to 1q23-25 (LOD = 3.78, empiric genome-wide<i>P</i> = .01). This region was not detected using the<i>DSM-IV</i>schizophrenia diagnosis, but has been strongly implicated in schizophrenia pathogenesis by previous linkage and association studies.Variants in the 1q region may specifically increase risk for a negative/deficit schizophrenia subtype. Alternatively, these results may reflect increased familiality/heritability of the negative class, the presence of multiple 1q schizophrenia risk genes, or a pleiotropic 1q risk locus or loci, with stronger genotype-phenotype correlation with negative/deficit symptoms. Using the second familial latent class, we identified nominally significant linkage to the original 10q peak region. <h3>Conclusion</h3> Genetic analyses of heritable, homogeneous phenotypes may improve the power of linkage and association studies of schizophrenia and thus have relevance to the design and analysis of genome-wide association studies." @default.
• W2094507913 created "2016-06-24" @default.
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• W2094507913 date "2009-10-01" @default.
• W2094507913 modified "2023-09-23" @default.
• W2094507913 title "Susceptibility Locus on Chromosome 1q23-25 for a Schizophrenia Subtype Resembling Deficit Schizophrenia Identified by Latent Class Analysis" @default.
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• W2094507913 doi "https://doi.org/10.1001/archgenpsychiatry.2009.136" @default.
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