Psychiatry Investig.  2016 Nov;13(6):630-636. 10.4306/pi.2016.13.6.630.

Linkage and Association Analyses of Schizophrenia with Genetic Variations on Chromosome 22q11 in Koreans

• Yoon SC
• Jang YL
• Kim JW
• Cho EY
• Park DY
• Hong KS
• Lee YS

• KMID: 2360380
• DOI: http://doi.org/10.4306/pi.2016.13.6.630

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, PRODH and ZDHHC8), 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.
CONCLUSION
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.

Keyword

Schizophrenia; Chromosome 22q11; Linkage; Association

MeSH Terms

Case-Control Studies
DNA
Gene Frequency
Genetic Markers
Genetic Variation*
Humans
Microsatellite Repeats
Polymorphism, Single Nucleotide
Sample Size
Schizophrenia*
DNA
Genetic Markers