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Clustering by neurocognition for fine mapping of the schizophrenia susceptibility loci on chromosome 6p |
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| Authors: | S-H Lin C -M Liu Y -L Liu C Shen-Jang Fann P -C Hsiao J -Y Wu S -I Hung C -H Chen H -M Wu Y -S Jou S K Liu T J Hwang M H Hsieh C -C Chang W -C Yang J -J Lin F H -C Chou S V Faraone M T Tsuang H -G Hwu W J Chen |
| Institution: | Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan; , Genetic Epidemiology Core Laboratory, Division of Genomic Medicine, Research Center for Medical Excellence, National Taiwan University, Taipei, Taiwan; , Department of Psychiatry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; , Division of Mental Health and Substance Abuse Research, National Health Research Institutes, Zhunan, Taiwan; , Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;;National Genotyping Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; , Institute of Statistical Science, Academia Sinica, Taipei, Taiwan;;Department of Mathematics, Tamkang University, Taipei, Taiwan; , Far Eastern Memorial Hospital, Taipei, Taiwan; , Molecular Medicine Program, Taiwan International Graduate Program, Academia Sinica, Taipei, Taiwan; , Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan;; Department of Psychiatry, Chimei Medical Center, Tainan, Taiwan; , Kai-Suan Psychiatric Hospital, Kaohsiung City, Taiwan; , Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA; , Harvard Institute of Psychiatric Epidemiology and Genetics, and Departments of Epidemiology and Psychiatry, Harvard University, Boston, Massachusetts, USA; , Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, California, USA; , and Department of Psychology, College of Science, National Taiwan University, Taipei, Taiwan |
| 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. |
| Keywords: | Candidate gene cluster analysis endophenotype executive dysfunction schizophrenia sustained attention deficit |