Table 2.
Association between non-HLA T1D candidate SNPs and development of IA, progression from IA to T1D, and development of T1D adjusted for HLA-DR3/4, DQB1*0302 genotype and first degree relative with T1D.
| SNP | Minor allele | Development of IA (n = 1619) |
Progression from IA to T1D (n = 132) |
Development of T1D (n = 1619) |
||||
|---|---|---|---|---|---|---|---|---|
| MAFa | Adjusted HRb and 95% CI | P value | Adjusted HRc and 95% CI | P value | Adjusted HRb and 95% CI | P value | ||
| C1QTNF6 (rs229541) | A | 0.44 | 1.57 (1.20, 2.05)d | 0.001 | 1.13 (0.75, 1.71)d | 0.56 | 1.95 (1.33, 2.87)d | 0.001 |
| C6orf173 (rs9388489) | G | 0.46 | 1.15 (0.88, 1.51)d | 0.31 | 0.87 (0.61, 1.24)d | 0.44 | 1.03 (0.69, 1.54)d | 0.87 |
| C14orf181 (rs1465788) | T | 0.28 | 0.97 (0.73, 1.27)d | 0.80 | 1.09 (0.62, 1.92)e | 0.77 | 0.70 (0.40, 1.23)e | 0.21 |
| IL2 (rs2069762) | C | 0.29 | 1.08 (0.82, 1.43)d | 0.58 | 1.22 (0.79, 1.87)d | 0.38 | 1.20 (0.79, 1.83)d | 0.40 |
| IL2 (rs4505848) | G | 0.35 | 1.04 (0.80, 1.34)d | 0.78 | 0.93 (0.67, 1.28)d | 0.65 | 1.18 (0.82, 1.70)d | 0.37 |
| IL2RA (rs12722563) | A | 0.12 | 0.90 (0.58, 1.41)e | 0.65 | 0.52 (0.17, 1.57)e | 0.25 | 0.43 (0.17, 1.08)e | 0.07 |
| IL2RA (rs2104286) | C | 0.27 | 0.85 (0.63, 1.15)d | 0.28 | 1.26 (0.70, 2.27)e | 0.44 | 0.77 (0.43, 1.38)e | 0.38 |
| IL7R (rs6897932) | T | 0.28 | 0.93 (0.68, 1.28)d | 0.66 | 0.86 (0.49, 1.53)e | 0.61 | 0.88 (0.50, 1.55)e | 0.65 |
| PRKCQ (rs947474) | G | 0.17 | 1.19 (0.80, 1.77)e | 0.40 | 0.76 (0.41, 1.42)e | 0.39 | 0.87 (0.47, 1.64)e | 0.67 |
| SKAP2 (rs7804356) | C | 0.25 | 0.90 (0.66, 1.22)d | 0.49 | 1.54 (0.83, 2.85)e | 0.17 | 1.01 (0.57, 1.78)e | 0.99 |
| SMARCE1 (rs7221109) | T | 0.35 | 0.94 (0.72, 1.22)d | 0.63 | 0.94 (0.57, 1.57)d | 0.82 | 0.73 (0.45, 1.20)d | 0.21 |
| TLR8 (rs5979785) | C | 0.20 | 0.82 (0.64, 1.05)d | 0.11 | 0.84 (0.61, 1.16)d | 0.29 | 0.86 (0.60, 1.24)d | 0.43 |
| UBASH3A (rs3788013) | A | 0.44 | 1.19 (0.89, 1.59)d | 0.25 | 1.03 (0.72, 1.48)d | 0.86 | 1.63 (1.04, 2.54)d | 0.03 |
| rs10517086 | A | 0.30 | ∗ | ∗ | 1.36 (0.77, 2.41)e | 0.30 | 2.03 (1.35, 3.03)d | 0.001 |
CI: confidence interval; DAISY: Diabetes Autoimmunity Study in the Young; HLA: human leukocyte antigen; HR: hazard ratio; IA: islet autoimmunity; MAF: minor allele frequency; T1D: type 1 diabetes.
aMinor allele frequency (MAF) calculated for children negative for IA.
bAdjusted for HLA-DR3/4, DQB1*0302 genotype and first degree relative with T1D. TLR8 (rs5979785) is additionally adjusted for sex because it is on the X chromosome.
cAdjusted for HLA-DR3/4, DQB1*0302 genotype, first degree relative with T1D, and age at first antibody positive visit. TLR8 (rs5979785) is additionally adjusted for sex because it is on the X chromosome.
dSNP analyzed additively with HR representing increase in risk for each additional minor allele.
eSNP analyzed dichotomously with HR representing increase in risk for at least one minor allele.
*SNP rs10517086 did not meet the assumptions of proportional hazards in the development of IA analysis and therefore was modeled using a restricted cubic spline (Figure 1).