Susceptibility locus on chromosome 1q23-25 for a schizophrenia subtype resembling deficit schizophrenia identified by latent class analysis

Holliday, Elizabeth G., McLean, Duncan E., Nyholt, Dale R., & Mowry, Bryan J. (2009) Susceptibility locus on chromosome 1q23-25 for a schizophrenia subtype resembling deficit schizophrenia identified by latent class analysis. Archives of General Psychiatry, 66(10), pp. 1058-1067.

View at publisher (open access)


Context: Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity.

Objective: To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes.

Design: Latent class and linkage analysis.

Setting: Taiwanese field research centers.

Participants: The latent class analysis included 1236 Han Chinese individuals with DSM-IV 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 (z = 2.88) on chromosome 10q22.3.

Main Outcome Measures: Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores.

Results: 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 P = .01). This region was not detected using the DSM-IV 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.

Conclusion: 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.

Impact and interest:

20 citations in Scopus
22 citations in Web of Science®
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 92004
Item Type: Journal Article
Refereed: Yes
Keywords: Adult, *Chromosome Mapping, Chromosomes, Human, Pair 1/*genetics, Diagnostic and Statistical Manual of Mental Disorders, Female, Genetic Heterogeneity, Genetic Linkage/genetics, Genetic Predisposition to Disease/*genetics, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Male, Models, Statistical, Multivariate Analysis, Phenotype, Psychiatric Status Rating Scales/statistics & numerical data, Schizophrenia/classification/*diagnosis/*genetics, Taiwan
DOI: 10.1001/archgenpsychiatry.2009.136
ISSN: 1538-3636
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2009 American Medical Association
Deposited On: 19 Jan 2016 00:28
Last Modified: 26 Jun 2017 20:01

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page