title: Linkage and Association Analyses of Schizophrenia with Genetic Variations on Chromosome 22q11 in Koreans.
abstract: OBJECTIVE
  Chromosome 22q11 has been implicated as a susceptibility locus of schizophrenia. It also contains various candidate genes for which evidence of association with schizophrenia has been reported. To determine whether genetic variations in chromosome 22q11 are associated with schizophrenia in Koreans, we performed a linkage analysis and case-control association study.
  
  
  METHODS
  Three microsatellite markers within a region of 4.35 Mb on 22q11 were genotyped for 47 multiplex schizophrenia families, and a non-parametric linkage analysis was applied. The association analysis was done with 227 unrelated patients and 292 normal controls. For 39 single nucleotide polymorphisms (SNPs) spanning a 1.4 Mb region (33 kb interval) containing four candidate schizophrenia genes (DGCR,COMT,PRODHandZDHHC8), allele frequencies were estimated in pooled DNA samples.
  
  
  RESULTS
  No significant linkage was found at any of the three microsatellite markers in single and multi-point analyses. Five SNPs showed suggestive evidence of association (p<0.05) and two more SNPs showed a trend for association (p<0.1) in pooled DNA association analysis. Individual genotyping was performed for those seven SNPs and four more intragenic SNPs. In this second analysis, all of the 11 SNPs individually genotyped did not show significant association.
  
  
  CONCLUSIONS
  The present study suggests that genetic variations on chromosome 22q11 may not play a major role in Korean schizophrenia patients. Inadequate sample size, densities of genetic markers and differences between location of genetic markers of linkage and association can contribute to an explanation of the negative results of this study.
authors.affiliation: Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Se Chang
authors.initials: SC
authors.lastname: Yoon
authors.affiliation: Department of Psychiatry, Seoul Medical Center, Seoul, Republic of Korea.
authors.forename: Yong Lee
authors.initials: YL
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine and Clinical Genetics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.affiliation: Department of Psychiatry, Seoul Mental Hospital, Seoul, Republic of Korea.
authors.forename: Dong Yeon
authors.initials: DY
authors.lastname: Park
authors.affiliation: Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Kyung Sue
authors.initials: KS
authors.lastname: Hong
authors.affiliation: Department of Psychiatry, Yong-In Mental Hospital, Yongin, Republic of Korea.
authors.forename: Yu Sang
authors.initials: YS
authors.lastname: Lee
keywords: Association; Chromosome 22q11; Linkage; Schizophrenia