Investigation of linkage and association/linkage disequilibrium of HLA A-, DQA1-, DQB1-, and DRB1-alleles in 69 sib-pair- and 89 trio-families with schizophrenia.
The hypothesis that HLA antigens confer susceptibility to schizophrenic disorders has been tested by studying linkage and association in a family sample with 69 sib-pair families. Suggestive evidence for linkage was obtained by nonparametric multipoint LOD score analysis with a maximum around DQB CAR (P = 0.0004), a microsatellite marker that is in linkage disequilibrium with the HLA antigen DQB1. Spurious evidence for negative association as calculated by the transmission disequilibrium test was found for HLA- DRB1*11 (chi-square = 11.72, corrected P value = 0.03) and for the haplotype DQB1*301-DQA1*501-DRB1*11 (chi-square = 11.3, corrected P value = 0.043). No evidence of association with these alleles was obtained in a sample of 89 trios with schizophrenic offspring and parents. Our results are not in favor of a direct involvement of the HLA system in development of schizophrenia, but are compatible with the possible existence of a susceptibility gene in the MHC region at chromosome 6p 21.31.
Schwab
Sibylle G
SG
Molecular Genetics Laboratory, Department of Psychiatry, University of Bonn, Bonn, Germany.
Hallmayer
Joachim
J
Freimann
Julia
J
Lerer
Bernard
B
Albus
Margot
M
Borrmann-Hassenbach
Margitta
M
Segman
Ronnen H
RH
Trixler
Matyas
M
Rietschel
Marcella
M
Maier
Wolfgang
W
Wildenauer
Dieter B
DB
D000483:Alleles; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D009679:Nuclear Family; D012559:Schizophrenia / Q000235:genetics*; D013223:Statistics as Topic
D015234:HLA-A Antigens; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006649:Histocompatibility Antigens; D004247:DNA