Evidence of Stage- and Age-Related Heterogeneity of Non-HLA SNPs and Risk of Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young

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)
		MAF^a	Adjusted HR^b and 95% CI	𝑃 value	Adjusted HR^c and 95% CI	𝑃 value	Adjusted HR^b 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).