The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History on the Progression From Multiple Autoantibodies to Type 1 Diabetes: A TEDDY Study Report
Article Figures & Tables
Figures
- Figure 1
Progression from multiple autoantibodies to T1D by FDR status (P = 0.39 from Cox regression).
- Figure 2
Progression from multiple autoantibodies to T1D by HLA-DR-DQ genotypes (P = 0.74 from Cox regression). FDR-specific HLA-DR-DQ genotypes are DR4/4b, DR4/1, DR4/13, DR4/9, and DR3/9.
- Figure 3
Progression from multiple autoantibodies to T1D by type of first autoantibody (Ab) (P = 0.02 from Cox regression).
- Figure 4
Progression from multiple autoantibodies to T1D by sex (P = 0.03 from Cox regression).
- Figure 5
Progression from multiple autoantibodies by number of minor alleles of SNPs within panels rs10517086_A (P = 0.03 from Cox regression) (A), rs1004446_A (P = 0.006 from Cox regression) (B), rs1534422_G (P = 0.006 from Cox regression) (C), and rs2327832_G (P = 0.03 from Cox regression) (D).
- Figure 6
Progression from multiple autoantibodies to T1D by number of minor alleles of SNP rs2327832_G in the subset of more than one autoantibody as first-appearing autoantibody (P < 0.001 from Cox regression).
Tables
- Table 1
Characteristics of children who progressed from multiple autoantibodies to T1D and those who did not
Did not progress to T1D Progressed to T1D Total, n (%) 222 (54) 190 (46) Country of residence, n (%) U.S. 82 (59) 57 (41) Finland 53 (48) 57 (52) Germany 16 (44) 20 (56) Sweden 71 (56) 56 (44) Family history of T1D, n (%) GP 171 (55) 140 (45) FDR: mother 12 (50) 12 (50) FDR: father 27 (50) 27 (50) FDR: sibling 12 (52) 11 (48) Sex, n (%) Female 88 (49) 92 (51) Male 134 (58) 98 (42) HLA-DR-DQ genotypes, n (%) DR3/4 121 (52) 110 (48) DR4/4 46 (61) 30 (39) DR4/8 31 (56) 24 (44) DR3/3 16 (53) 14 (47) FDR specific 8 (40) 12 (60) Age at multiple persistent confirmed IA (months), median (IQR) 48 (31–74) 21 (15–31) Type of first autoantibody, n (%) GADA only 85 (66) 43 (34) IAA only 84 (53) 76 (47) Two or more autoantibodies 49 (42) 68 (58) IA-2A only 4 (57) 3 (43) FDR-specific HLA-DR-DQ genotypes are DR4/4b, DR4/1, DR4/13, DR4/9, and DR3/9.
- Table 2
Cox regression analysis of risk factors for progression from multiple autoantibodies to T1D
HR (95% CI) P Age at multiple autoantibodies onset (months) 0.96 (0.95, 0.97) <0.001 HLA-DR-DQ genotype 0.74 DR3/4 1.24 (0.79, 1.93) 0.35 DR4/4 1 [Reference] DR4/8 1.22 (0.68, 2.18) 0.50 DR3/3 1.44 (0.70, 2.96) 0.32 FDR specific 1.58 (0.73, 3.41) 0.25 Family history of T1D 0.69 FDR: mother 1.34 (0.66, 2.75) 0.42 FDR: father 1.30 (0.80, 2.09) 0.29 FDR: sibling 0.98 (0.48, 2.01) 0.96 GP 1 [Reference] Type of first autoantibody 0.02 GADA only 1.16 (0.76, 1.78) 0.49 IAA only 1 [Reference] Two or more autoantibodies 1.66 (1.15, 2.39) 0.006 Sex Female 1.43 (1.04, 1.96) 0.03 Male 1 [Reference] Country of residence 0.84 U.S. 1 [Reference] Finland 1.05 (0.53, 2.10) 0.89 Germany 1.13 (0.59, 2.14) 0.71 Sweden 0.88 (0.58, 1.34) 0.55 SNP rs1004446_A (INS) 0.71 (0.55, 0.91) 0.006 SNP rs10517086_A 1.31 (1.03, 1.67) 0.03 SNP rs1534422_G 1.39 (1.10, 1.76) 0.006 SNP rs2327832_G (TNFAIP3) 1.34 (1.03, 1.74) 0.03 PC1 1.11 (0.91, 1.35) 0.32 PC2 0.96 (0.72, 1.28) 0.78 The top two principal components (PC1 and PC2) from the principal components analysis on Immunochip data were included as covariates to correct for population stratification. FDR-specific HLA-DR-DQ genotypes are DR4/4b, DR4/1, DR4/13, DR4/9, and DR3/9.
In this Issue
