Fine Mapping of the Schizophrenia Susceptibility Loci on Chromosome 6p24.3 and 6p22.3: A Family-Based Association Study
Date Issued
2007
Date
2007
Author(s)
Lin, Sheng-Hsiang
DOI
en-US
Abstract
Two studies were to conduct a fine mapping of the schizophrenia susceptibility loci near the D6S296 and D6S274 regions using single nucleotide polymorphism (SNP) markers by neuropsychological measures as endophenotypes of the disease.
Study 1. Fine Mapping of the Schizophrenia Susceptibility Loci on Chromosome 6p24.3 and 6p22.3: A Two-Stage Family-Based Association Study
Objective. To identify vulnerability genes of schizophrenia near D6S296 region of chromosome 6p24.3 and D6S274 region of chromosome 6p22.3 using SNP fine mapping study.
Methods. We used the 64 SNPs around 2 cM of the D6S296 and D6S296 to analyze both the single locus and haplotype markers in 216 schizophrenic families with at least 2 affected siblings. The two-stage association analyses have further carried out in the subgroups of schizophrenia defined by neuropsychological deficits of sustained attention and executive function, respectively.
Results. We found that haplotype rs1225934-rs13878 on BMP6-TXNDC5 genes was significant in the whole sample as well as the subgroups of schizophrenia defined by the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST) deficits, respectively. In particular, the association of rs1225934-rs13878 with schizophrenia became more pronounced for the subgroups with neuropsychological deficits (i.e., deficits in d' on the degraded CPT and deficits in the Categories Achieved on the WCST).
Conclusions. We consider these two genes may have etiological roles in schizophrenia, especially in the subgroup defined by CPT and WCST deficits, respectively and are worth for further replication studies.
Study 2. Family-Based Clustering by Neruopsychological Functioning for Fine-Mapping of the Schizophrenia Susceptibility Loci on Chromosome 6p24.3 and 6p22.3
Objective. Because of the heterogeneity and inconsistent findings regarding genetic research of schizophrenia, using endophenotypes to refine the phenotype characterization has been advocated. The aim of the study was to obtain deficit and non-deficit family clusters by means of neuropsychological measures for genetic association analyses.
Methods. Eight neuropsychological test scores of the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST) from 155 schizophrenic families comprising at least two affected siblings and were performed in a cluster analysis with data visualization. Then the deficit and non-deficit family clusters from the cluster approach were used in fine mapping of D6S296 and D6S274.
Results. The scores of the deficit cluster were more impaired than those of the non-deficit cluster in all neuropsychological measures. We found rs1225934-rs13873 on BMP6-TXNDC5 genes was significant in deficit cluster by the two-stage association analysis.
Conclusions. The classification strategy may provide for selecting more homogeneous groups of families into subsequent genetic analyses. The results support that a susceptibility locus conferring vulnerability to schizophrenia with neuropsychological impairment may be near rs1225934-rs13878 on BMP6-TXNDC5.
Subjects
精神分裂症
內在表現型
持續注意力缺失
執行功能障礙
候選基因
集群分析
Endophenotype
Sustained attention deficit
Executive dysfunction
Candidate gene
Cluster analysis
Type
thesis
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