A Cross-Validation Design Using Age and HLA Alleles for the Assessment of Clinical Schizophrenia Risk.
BACKGROUND
Schizophrenia (SCH) is a highly heritable disease that occurs mostly in young adults. Genetic factors usually play important roles in the onset of SCH. Human leukocyte antigen complex (HLA) genes are considered to be the important genetic predisposition factor and the genetic markers in SCH and other diseases.


METHODS
To screen SCH-associated HLA alleles, alleles for HLA-DRB1 and HLA-DQB1 loci were determined using the PCR-SSP typing kit. Statistically significant differences between observed and expected frequencies of allele combinations were identified. To further determine allele combinations related to SCH, an analysis of the age of onset of SCH in the patient who carried an allele or specific allele combination was conducted. Finally, a crossvalidation of the two sets of analytical results was carried out. Statistical differences in frequency values between the SCH group and the control population were observed for five HLA alleles.


RESULTS
The results of cross-validation showed that there was a significant difference for a combination of DRB1*07 and DQB1*02, whereas no significant differences were observed for the other four alleles.


CONCLUSIONS
We suggested that the combination of DRB1*07-DQB1*02 may be related to SCH susceptibility. The cross-validation design using age and HLA alleles could enable additional discoveries pertaining to the relationship between specific HLA allele combinations at different loci and the onset of complex diseases.
Song
S
Laiyu
Zhang
Z
Lei
Xie
X
Soufu
Xv
X
Junting
Zhou
Z
Jie
Liu
L
Hui
D000328:Adult; D000367:Age Factors; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D040941:Heredity; D006801:Humans; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D005819:Genetic Markers; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C456920:HLA-DRB1*07 antigen