Table 3.
Association between factors and risk of progression from single autoantibody to multiple autoantibodies and from multiple autoantibodies to type 1 diabetes
| Factor | Comparison | Single autoantibody to multiple autoantibodies | Multiple ab+ to type 1 diabetes, overall (n/N = 283/480) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Overall (n/N = 346/701) | Subgroup by autoantibody at seroconversion | ||||||||
| IAA-first (n/N = 167/308) | GADA-first (n/N = 168/370) | ||||||||
| HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | ||
| Autoantibody at seroconversion | IA-2A vs. GADA | 1.12 (0.57, 2.22) | 0.736 | ||||||
| IAA vs. GADA | 1.00 (0.77, 1.29) | 0.992 | |||||||
| Initial ab | Multiple vs. single ab+ | 1.91 (1.42, 2.56) | <0.001 | ||||||
| Age (years) at seroconversion* | 0.65 (0.57, 0.75) | <0.001 | 0.63 (0.51, 0.77) | <0.001 | 0.64 (0.52, 0.80) | <0.001 | 0.62 (0.51, 0.75) | <0.001 | |
| Sex | Male vs. female | 1.04 (0.82, 1.31) | 0.752 | 1.04 (0.72, 1.51) | 0.823 | 0.89 (0.63, 1.26) | 0.505 | 0.63 (0.49, 0.83) | 0.001 |
| Family history | FDR father vs. GP | 1.42 (1.00, 2.01) | 0.049 | 1.52 (0.91, 2.54) | 0.111 | 1.35 (0.80, 2.27) | 0.260 | 0.99 (0.65, 1.51) | 0.970 |
| FDR sibling vs. GP | 1.73 (1.05, 2.85) | 0.031 | 1.97 (1.01, 3.86) | 0.047 | 0.97 (0.32, 2.97) | 0.958 | 1.36 (0.77, 2.39) | 0.290 | |
| FDR mother vs. GP | 1.50 (0.83, 2.71) | 0.182 | 1.81 (0.70, 4.65) | 0.219 | 1.37 (0.60, 3.12) | 0.460 | 1.55 (0.88, 2.74) | 0.127 | |
| HLA genotype | DR3/4 vs. DR3/3 | 2.63 (1.75, 3.94) | <0.001 | 5.42 (1.66, 17.67) | 0.005 | 2.44 (1.52, 3.92) | <0.001 | 1.12 (0.66, 1.89) | 0.680 |
| DR4/4 vs. DR3/3 | 2.28 (1.44, 3.60) | <0.001 | 5.82 (1.74, 19.48) | 0.004 | 1.84 (1.03, 3.30) | 0.041 | 1.00 (0.56, 1.79) | 0.987 | |
| DR4/8 vs. DR3/3 | 1.80 (1.09, 2.96) | 0.021 | 3.93 (1.17, 13.22) | 0.027 | 1.93 (0.95, 3.93) | 0.070 | 0.89 (0.48, 1.67) | 0.724 | |
| FDR specific vs. DR3/3 | 2.09 (0.98, 4.47) | 0.057 | 4.74 (1.16, 19.40) | 0.030 | 3.82 (0.80, 18.18) | 0.092 | 1.37 (0.59, 3.16) | 0.458 | |
| Country | Finland vs. U.S. | 1.29 (0.84, 1.97) | 0.246 | 1.62 (0.89, 2.94) | 0.113 | 1.22 (0.61, 2.40) | 0.575 | 1.02 (0.63, 1.67) | 0.931 |
| Germany vs. U.S. | 0.69 (0.40, 1.18) | 0.177 | 0.75 (0.36, 1.56) | 0.447 | 0.71 (0.27, 1.90) | 0.496 | 1.24 (0.72, 2.14) | 0.432 | |
| Sweden vs. U.S. | 0.69 (0.52, 0.93) | 0.014 | 0.74 (0.46, 1.18) | 0.202 | 0.69 (0.46, 1.05) | 0.081 | 0.82 (0.59, 1.16) | 0.266 | |
| rs689_A (INS) | 0.70 (0.56, 0.88) | 0.002 | 0.83 (0.58, 1.18) | 0.292 | 0.62 (0.44, 0.86) | 0.005 | 1.05 (0.81, 1.36) | 0.704 | |
| rs2476601_A (PTPN22) | 1.31 (1.05, 1.63) | 0.017 | 1.08 (0.79, 1.49) | 0.631 | 1.79 (1.30, 2.47) | <0.001 | 1.15 (0.88, 1.51) | 0.307 | |
| rs3184504_T (SH2B3) | 0.98 (0.84, 1.15) | 0.809 | 0.91 (0.71, 1.17) | 0.467 | 1.08 (0.85, 1.38) | 0.531 | 1.02 (0.85, 1.22) | 0.834 | |
| rs12708716_G (CLEC16A) | 0.88 (0.73, 1.05) | 0.157 | 0.80 (0.59, 1.07) | 0.126 | 0.98 (0.74, 1.29) | 0.864 | 1.19 (0.97, 1.45) | 0.095 | |
| rs2292239_T (ERBB3) | 1.12 (0.94, 1.34) | 0.212 | 1.08 (0.80, 1.46) | 0.633 | 1.12 (0.87, 1.44) | 0.397 | 1.08 (0.89, 1.31) | 0.444 | |
| rs763361_A (CD226) | 0.86 (0.73, 1.01) | 0.070 | 0.84 (0.67, 1.07) | 0.158 | 1.00 (0.78, 1.29) | 1.000 | 1.12 (0.92, 1.35) | 0.265 | |
| rs1990760_G (IFIH1) | 0.99 (0.83, 1.18) | 0.928 | 1.22 (0.93, 1.59) | 0.145 | 0.87 (0.67, 1.12) | 0.282 | 1.12 (0.92, 1.37) | 0.255 | |
| rs11203203_A (UBASH3A) | 1.19 (1.01, 1.40) | 0.041 | 1.01 (0.77, 1.33) | 0.930 | 1.35 (1.06, 1.72) | 0.014 | 1.05 (0.87, 1.27) | 0.613 | |
| rs4948088_A (COBL) | 0.83 (0.52, 1.33) | 0.440 | 1.01 (0.47, 2.20) | 0.977 | 0.77 (0.41, 1.45) | 0.418 | 1.27 (0.77, 2.09) | 0.343 | |
| rs2327832_G (TNFAIP3) | 0.91 (0.74, 1.13) | 0.419 | 0.81 (0.58, 1.12) | 0.199 | 0.98 (0.70, 1.37) | 0.904 | 1.40 (1.12, 1.74) | 0.003 | |
| rs7202877_C (CTRB2) | 1.00 (0.79, 1.27) | 0.999 | 0.96 (0.68, 1.34) | 0.805 | 1.13 (0.78, 1.64) | 0.512 | 1.13 (0.86, 1.47) | 0.382 | |
| rs11258747_A (PRKCQ) | 1.10 (0.92, 1.33) | 0.298 | 1.14 (0.86, 1.51) | 0.365 | 1.04 (0.80, 1.36) | 0.749 | 0.96 (0.78, 1.18) | 0.713 | |
| rs12251307_A (RBM17, IL2RA) | 0.68 (0.51, 0.90) | 0.007 | 0.81 (0.54, 1.22) | 0.314 | 0.61 (0.39, 0.94) | 0.026 | 1.03 (0.77, 1.39) | 0.839 | |
| rs11755527_C (BACH2) | 1.11 (0.94, 1.30) | 0.224 | 1.44 (1.12, 1.84) | 0.004 | 0.92 (0.72, 1.19) | 0.546 | 0.85 (0.70, 1.03) | 0.101 | |
| rs7804356_G (SKAP2) | 0.87 (0.71, 1.07) | 0.189 | 0.92 (0.68, 1.23) | 0.574 | 0.72 (0.52, 0.98) | 0.038 | 1.26 (1.01, 1.58) | 0.043 | |
| rs12444268_A | 1.25 (1.05, 1.50) | 0.014 | 1.45 (1.09, 1.92) | 0.010 | 1.08 (0.83, 1.40) | 0.557 | 0.88 (0.71, 1.08) | 0.219 | |
| rs1534422_G (MIR3681HG) | 0.90 (0.76, 1.06) | 0.192 | 0.73 (0.56, 0.94) | 0.016 | 0.91 (0.71, 1.16) | 0.428 | 1.32 (1.09, 1.60) | 0.005 | |
| rs3825932_A (CTSH) | 0.92 (0.78, 1.08) | 0.306 | 0.83 (0.65, 1.06) | 0.139 | 1.01 (0.80, 1.29) | 0.907 | 0.76 (0.62, 0.93) | 0.007 | |
| rs1004446_A (INS) | 0.91 (0.75, 1.09) | 0.304 | 0.85 (0.64, 1.13) | 0.263 | 1.09 (0.82, 1.46) | 0.554 | 0.81 (0.65, 1.00) | 0.053 | |
| PC1† | 1.17 (0.95, 1.45) | 0.137 | 1.03 (0.78, 1.36) | 0.838 | 1.42 (0.99, 2.03) | 0.059 | 0.77 (0.60, 0.99) | 0.044 | |
| PC2† | 1.19 (0.98, 1.45) | 0.075 | 1.30 (1.04, 1.63) | 0.024 | 1.10 (0.78, 1.54) | 0.597 | 0.94 (0.75, 1.19) | 0.604 | |
Adjusted HRs were estimated from multivariable proportional hazards models. ab, autoantibody; Multiple ab+, positive for multiple autoantibodies; Multiple vs. single ab+, positive for multiple autoantibodies or a single autoantibody.
*
Age at seroconversion was log-transformed.
†
PC1 and PC2 were the top two principal components estimated from the Immunochip data. GP, general population (i.e., no affected first-degree relative).