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 3

Non-HLA T1D candidate SNPs associated with development of IA, progression from IA to T1D, and/or development of T1D in DAISY.

SNP	Development of IA		Progression from IA to T1D		Development of T1D
	Adjusted HR and 95% CI	𝑃 value	Adjusted HR and 95% CI	P value	Adjusted HR and 95% CI	𝑃 value
C1QTNF6 (rs229541)	1.57 (1.20, 2.05 )^𝐚𝐛𝐜	0.001	1.13 (0.75, 1.71)^abd	0.56	1.95 (1.33, 2.87 )^𝐚𝐛𝐜	0.001
CTLA4 (rs231775)	1.12 (0.86, 1.46)^aef	0.42	0.54 (0.33, 0.88 )^𝐚𝐞𝐠	0.01	1.00 (0.70, 1.43)^ahc	1.00
INS (rs689)	1.39 (0.99, 1.95)^aef	0.05	1.34 (0.72, 2.52)^aeg	0.35	1.75 (1.08, 2.83 )^𝐚𝐡𝐜	0.02
PTPN2 (rs1893217)	1.42 (1.02, 1.99 )^𝐚𝐜𝐡	0.04	0.65 (0.27, 1.60)^ijk	0.35	0.99 (0.60, 1.66)^ach	0.98
PTPN22 (rs2476601)	1.83 (1.27, 2.63 )^𝐚𝐞𝐟	0.001	0.98 (0.50, 1.93)^aeg	0.96	1.74 (1.04, 2.90 )^𝐚𝐡𝐜	0.03
UBASH3A (rs11203203)	1.46 (1.11, 1.91 )^𝐚𝐜𝐡	0.01	**	**	1.83 (1.28, 2.64 )^𝐚𝐜𝐡	0.001
UBASH3A (rs3788013)	1.19 (0.89, 1.59)^abc	0.25	1.03 (0.72, 1.48)^abd	0.86	1.63 (1.04, 2.54 )^𝐚𝐛𝐜	0.03
rs10517086	*	*	1.36 (0.77, 2.41)^bdj	0.30	2.03 (1.35, 3.03 )^𝐚𝐛𝐜	0.001

DAISY: Diabetes Autoimmunity Study in the Young; HLA: human leukocyte antigen; HR: hazard ratio; CI: confidence interval; IA: islet autoimmunity; T1D: type 1 diabetes.
^aSNP analyzed additively with HR representing increase in risk for each additional minor allele.
^bListed in Table 2 of the current paper.
^cAdjusted for HLA-DR3/4, DQB1*0302 genotype and first degree relative with T1D.
^dAdjusted for HLA-DR3/4, DQB1*0302 genotype, first degree relative with T1D, and age at first antibody positive visit.
^eFrom Steck et al. (2009) [9].
^fAdjusted for HLA-DR3/4, DQB1*0302 genotype, ethnicity, sex, and first degree relative with type 1 diabetes.
^gAdjusted for HLA-DR3/4, DQB1*0302 genotype, ethnicity, sex, first degree relative with type 1 diabetes, and age at first antibody positive visit.
^hFrom Steck et al.(2012) [11].
ⁱFrom Frederiksen et al. (2013) [12]. Frederiksen et al. (2013) [12] did not find an association between PTPN2 (rs1893217) and development of IA, which can be attributed to the use of different IA case definitions used in the manuscripts by Steck et al. (2009) [9] and Frederiksen et al. (2013) [12].
^jSNP analyzed dichotomously with HR representing increase in risk for at least one minor allele.
^kAdjusted for PTPN2 (rs478582), HLA-DR3/4, DQB1*0302 genotype, first degree relative with type 1 diabetes, ethnicity, and age at first IA positive visit.
**Analysis not conducted.
*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 of the current paper).