Family‐based association study of schizophrenia with 444 markers and analysis of a new susceptibility locus mapped to 11q13.3

Abstract

Family-based linkage disequilibrium (LD) mapping has been suggested as a powerful and practical alternative to linkage analysis. We have performed a genome-wide LD survey of susceptibility loci for schizophrenia in a Japanese population. We first typed 119 schizophrenic pedigrees (357 individuals) using 444 microsatellite markers, and analyzed the data using the pedigree disequilibrium test. This analysis revealed 14 markers demonstrating significant transmission distortion. To corroborate these findings, the statistical methods were changed to the extended transmission disequilibrium test (ETDT), using 80 independent complete trios (schizophrenic proband and both parents), with 68 derived from initial pedigrees and 12 newly recruited trios. ETDT supported two markers for continued association, D11S987 on 11q13.3 (P = 0.00009) and D16S423 on 16p13.3 (P = 0.002). We scrutinized the most significant genomic locus on 11q11-13 by adding 26 new markers for analysis. Results of three-marker haplotype analysis in the region showed evidence of association with schizophrenia (most significant haplotype P = 0.0005, global P = 0.022). Although the present study may have missed other potential genomic intervals because of the sparse mapping density, we hope that it has identified promising anchor points for further studies to identify risk-conferring genes for schizophrenia in the Japanese population. In addition, we provide useful information on genomic LD structures in Japanese populations, which can be used for LD mapping of complex diseases.

Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach

“…Cyclin D1 maps to a locus on 11q13.3 that has been linked to bipolar disorder 117 and schizophrenia. 118 Last but not least, cyclin D1 gene expression was reported to be altered in post-mortem brains of human alcoholics. 59 Our data also show that alcohol-preferring rats have lower baseline levels of FYN and IGF1R than alcohol-non-preferring rats in the NAC, and that these levels are decreased by the ICSA of alcohol in the VTA ( Table 3).…”

The myelin-pathogenesis puzzle in schizophrenia: a literature review

“…67 Moreover, an investigation of linkage disequilibrium using 444 microsatellite markers in a Japanese sample identified 11q13 as a potential liability locus for schizophrenia, adding further interest in this area. 68 Chromosomes 13 and 14 Several molecular studies have replicated linkage locations on the long arm of chromosome 13 10,36 and highlighted putative susceptibility genes in this area. 69,70 The D-amino acid oxidase activator (DAOA; formerly known as G72) gene is regarded as a very promising candidate to the genetic risk for the disorder.…”

Are There Schizophrenia Genetic Markers and Mutations? A Systematic Review and Meta-Analyses

“…The NFKB3 located on chromosome 11q13 showed a suggestive linkage to schizophrenia in a family-based linkage disequilibrium analysis in a Japanese population [69].…”

“…A GWAS study in Caucasian population showed significant association with schizophrenia were in a region of LD on chromosome 6p22.1, including several immunity related genes other than the RELA gene [69]. However, the biological significance of this gene in susceptibility for schizophrenia might not be large, because 22% of the patients with schizophrenia have homozygous of risk allele in SNP4, but 16% of the controls also are homozygous of risk allele in SNP4.…”