TABLE 2.
Associations at 24 non-HLA loci in a maximum of 1,196 autoimmune diabetic case subjects diagnosed at over 17 years of age and 2,215 control subjects
| Candidate gene (region), SNP |
N Chromosomes (MAF) |
OR [95% CI] | P | Power* |
||
|---|---|---|---|---|---|---|
| Case subjects | Control subjects | α = 0.001 | α = 0.05 | |||
| PTPN22 (1p13.2), rs2476601 (C>T) | 376 (0.16) | 431 (0.10) | 1.77 [1.53–2.06] | 8.03 × 10−14 | 1.00 | 1.00 |
| IFIH1 (2q24.2), rs1990760 (A>G) | 832 (0.36) | 1,643 (0.39) | 0.87 [0.78–0.96] | 0.0077 | 0.35 | 0.83 |
| STAT4 (2q32.2), rs7574865 (G>T) | 590 (0.25) | 938 (0.21) | 1.23 [1.09–1.39] | 5.93 × 10−4 | 0.04 | 0.35 |
| CTLA4 (2q33.2), rs3087243 (G>A) | 928(0.39) | 2,043 (0.46) | 0.75 [0.68–0.83] | 3.65 × 10−8 | 0.74 | 0.98 |
| IL2 (4q27), rs2069763 (G>T) | 786(0.34) | 1,484 (0.34) | 0.96 [0.86–1.08] | 0.51 | 0.17 | 0.64 |
| IL2 (4q27), rs2069762 (T>G) | 715 (0.30) | 1,366 (0.31) | 0.96 [0.86–1.08] | 0.51 | 0.12 | 0.57 |
| BACH2 (6q15), rs11755527 (C>G) | 1,144 (0.49) | 1,686 (0.45) | 1.16 [1.05–1.29] | 0.0045 | 0.20 | 0.68 |
| GLIS3 (9p24.2), rs7020673 (G>C) | 1,052 (0.44) | 2,083 (0.48) | 0.88 [0.79–0.97] | 0.012 | 0.23 | 0.72 |
| IL2RA (10p15.1), rs12722495 (A>G) | 190 (0.08) | 499 (0.11) | 0.70 [0.58–0.83] | 5.22 × 10−5 | 0.99 | 1.00 |
| IL2RA (10p15.1), rs2104286 (A>G) | 523 (0.22) | 1,083 (0.25) | 0.85 [0.76–0.96] | 0.031 | 0.07 | 0.44 |
| IL2RA (10p15.1), rs11594656 (T>A) | 576 (0.25) | 1,127 (0.27) | 0.92 [0.82–1.03] | 0.13 | 0.20 | 0.68 |
| RNLS (10q23.31), rs10509540 (T>C) | 530 (0.24) | 1,133 (0.26) | 0.88 [0.78–1.00] | 0.041 | 0.95 | 1.00 |
| INS (11p15.5), rs689 (A>T) | 382 (0.16) | 1,280 (0.29) | 0.47 [0.42–0.54] | 1.97 × 10−32 | 1.00 | 1.00 |
| ERBB3 (12q13.2), rs2292239 (C>A) | 846 (0.36) | 1,376 (0.32) | 1.20 [1.08–1.33] | 8.40 × 10−4 | 0.97 | 100 |
| SH2B3 (12q24.12), rs3184504 (A>G) | 1,030 (0.44) | 2,114 (0.48) | 1.35 [1.22–1.50] | 2.67 × 10−9 | 0.95 | 100 |
| CLEC16A (16p13.13), rs12708716 (A>G) | 763 (0.34) | 1,583 (0.38) | 0.83 [0.75–0.93] | 7.82 × 10−4 | 0.77 | 0.98 |
| IL27 (16p11.2), rs4788084 (G>A) | 939 (0.39) | 1,830 (0.42) | 0.90 [0.81–1.00] | 0.042 | 0.37 | 0.84 |
| CTRB2 (16q23.1), rs7202877 (T>G) | 271 (0.12) | 468 (0.10) | 1.09 [0.92–1.27] | 0.32 | 0.41 | 0.86 |
| GSDMB (17q12), rs2290400 (G>A) | 1,127 (0.49) | 2,115 (0.50) | 0.97 [0.87–1.07] | 0.051 | 0.30 | 0.79 |
| PTPN2 (18p11.21), rs478582 (T>C) | 1,027 (0.43) | 1,947 (0.44) | 0.96 [0.87–1.06] | 0.55 | 0.65 | 0.96 |
| PTPN2 (18p11.21), rs45450798 (G>C) | 390 (0.17) | 644 (0.15) | 1.15 [1.00–1.31] | 0.054 | 0.63 | 0.95 |
| CD226 (18q22.2), rs763361 (C>T) | 1,157 (0.49) | 2,178 (0.49) | 0.98 [0.89–1.08] | 0.68 | 0.25 | 0.74 |
| UBASH3A (21q22.3), rs3788013 (C>A) | 1,035 (0.44) | 1,853 (0.42) | 1.06 [0.96–1.17] | 0.26 | 0.19 | 0.68 |
| Obesity locus | ||||||
| FTO (16q12.2), rs9939609 (T>A)† | 953 (0.41) | 1,798 (0.42) | 0.96 [0.87–1.06] | 0.45 | 0.42 | 0.86 |
| Type 2 diabetes locus | ||||||
| TCF7L2 (10q25.2), rs12255372 (G>T) | 571 (0.27) | 1,147 (0.27) | 1.01 [0.89–1.13] | 0.93 | 0.99 | 0.99 |
| Autoantibody loci | ||||||
| GAD2 (10p12.1), rs2839671 (G>A) | 412 (0.18) | 776 (0.18) | 0.96 [0.84–1.09] | 0.50 | 0.13 | 0.59 |
| FCRL3 (1q23.1), rs7528684 (A>G) | 1,045 (0.44) | 1,919 (0.44) | 1.03 [0.93–1.14] | 0.58 | 0.30 | 0.79 |
MAF, minor allele frequency; number of chromosomes is listed for the minor allele.
*Power is calculated for the susceptible allele, assuming multiplicative allelic effects at all loci except INS. For all type 1 diabetes–associated loci, the effect estimates and minor allele frequencies used to calculate the power were taken from Smyth et al. (38), Fung et al. (39), and Barrett et al. (1) and are also available from www.t1dbase.org/page/regions. Note that if the association of a locus is reduced with increasing age at diagnosis, these power estimates could be inflated. For the TCF7L2 and FTO loci, the effect estimates as reported for type 2 diabetes were used (40,41). For the autoantibody loci, an effect estimate of 1.15, which is not unusual for type 1 diabetes, was used.
†rs9939609 is in LD with rs9931494, the SNP reported as associated with LADA (r2 = 0.91, D′ = 0.98 in Centre d'Etude du Polymorphisme Humaine samples) (14).