Clustering by neurocognition for fine mapping of the schizophrenia susceptibility loci on chromosome 6p
Journal
Genes, Brain and Behavior
Journal Volume
8
Journal Volume
8
Journal Issue
8
Journal Issue
8
Pages
785-794
Start Page
785
End Page
794
ISSN
1601-183X
Date Issued
2009-11
Author(s)
Lin S.-H.
Liu Y.-L.
Shen-Jang Fann C.
Hsiao P.-C.
Wu J.-Y.
Hung S.-I.
Chen C.-H.
Wu H.-M.
Jou Y.-S.
Liu S.K.
Chang C.-C.
Yang W.-C.
Lin J.-J.
Chou F.H.-C.
Faraone S.V.
Tsuang M.T.
Abstract
Chromosome 6p is one of the most commonly implicated regions in the genome-wide linkage scans of schizophrenia, whereas further association studies for markers in this region were inconsistent likely due to heterogeneity. This study aimed to identify more homogeneous subgroups of families for fine mapping on regions around markers D6S296 and D6S309 (both in 6p24.3) as well as D6S274 (in 6p22.3) by means of similarity in neurocognitive functioning. A total of 160 families of patients with schizophrenia comprising at least two affected siblings who had data for eight neurocognitive test variables of the continuous performance test (CPT) and the Wisconsin card sorting test (WCST) were subjected to cluster analysis with data visualization using the test scores of both affected siblings. Family clusters derived were then used separately in family-based association tests for 64 single nucleotide polymorphisms (SNPs) covering the region of 6p24.3 and 6p22.3. Three clusters were derived from the family-based clustering, with deficit cluster 1 representing deficit on the CPT, deficit cluster 2 representing deficit on both the CPT and the WCST, and a third cluster of nondeficit. After adjustment using false discovery rate for multiple testing, SNP rs13873 and haplotype rs1225934-rs13873 on BMP6-TXNDC5 genes were significantly associated with schizophrenia for the deficit cluster 1 but not for the deficit cluster 2 or nondeficit cluster. Our results provide further evidence that the BMP6-TXNDC5 locus on 6p24.3 may play a role in the selective impairments on sustained attention of schizophrenia. ? 2009 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society.
SDGs
Other Subjects
adult; article; attention disturbance; chromosome 6p; cognition; controlled study; disease association; family assessment; female; gene cluster; gene locus; gene mapping; haplotype; human; major clinical study; male; marker gene; mental patient; mental test; priority journal; schizophrenia; sibling; single nucleotide polymorphism; Wisconsin Card Sorting Test; Adult; Aged; Bone Morphogenetic Protein 6; Brain; Chromosome Mapping; Chromosomes, Human, Pair 6; Cluster Analysis; Cognition Disorders; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Male; Middle Aged; Neuropsychological Tests; Phenotype; Polymorphism, Single Nucleotide; Protein Disulfide-Isomerases; Schizophrenia; Schizophrenic Psychology
Type
journal article