Table 1.
Association results (from 499 Graves' disease cases and 504 controls) of the four alleles with Bonferroni corrected P value smaller than 0.05.
Table 2.
Replication with our family-based study and/or previous studies in Asians.
Figure 1.
Linkage disequilibrium analysis of HLA-B, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles showing significant associations with GD.
The distances between consecutive loci are approximately 1225 Kb, 81 kb and 416 Kb respectively. The r2 value (× 100) of any allele pair was plotted inside the corresponding cell. Except for strong linkage disequilibrium (r2 = 0.48 in controls, r2 = 0.62 in cases) between DRB1*16:02 and DQB1*05:02, in general the r2 value between other alleles was quite low.
Table 3.
Analysis of DPB1*05:01 genotype distribution and odds ratio.
Figure 2.
Receiver operating characteristics (ROC) curve for the logistic regression model.
Disease = −3.6802+0.4487×B*46:01+0.8883×DPB1*05:01 – 0.3494×DQB1*03:02 – 0.492×DRB1*12:02+0.8388×DRB1*15:01+1.0727×DRB1*16:02+1.5865×Female. The logistic regression model was built based on the data from our unrelated case-control study individuals. Genotypes were coded following a dominant inheritance mode. The area under curve (AUC) of this ROC curve is 0.75.
Table 4.
Population-attributable risk percentage of seven associated alleles and one haplotype under dominant model.
Figure 3.
Allele frequency variations of HLA-DPB1*05:01 and HLA-DRB1*03:01 across worldwide populations.
The allele frequencies (×100%) are presented with different colors, shown as the color bar below the figure. (A) HLA-DPB1*05:01, the major GD susceptibility allele we demonstrated, is much more prevalent in Asians than in Caucasians. (B) HLA-DRB1*03:01, the major GD susceptibility allele in Caucasians, has low frequencies in Asians. The data were screenshots from New Allele Frequency Database: http://www.allelefrequencies.net [33] with permission.