Table 2.

Follow up analysis of the genome-wide association scan of 13,378 nonsynonymous SNPs in type 1 diabetes

Chr	Gene	SNP	Cases and controls							Families		Overall P-values
			nsSNP results (3,400 affected individuals, 3,300 controlsa)			Follow-up (2,700 affected individuals, 3,500 controls)		All (6,100 affected individuals, 6,800 controls)		Follow-up (2,997 parent-child trios)		Follow-up samples	All samples
			MAF	1-d.f. test P	OR (95% c.i.)	1-d.f. test P	OR (95% c.i.)	1-d.f. test P	OR (95% c.i.)	TDT Pb	RR (95%c.i.)	P	P
1p13	PTPN22	rs2476601 (R620W)	0.0939	3.26 × 10−37	1.99 (1.79– 2.22)	1.69 × 10−32	2.04 (1.81– 2.29)	2.71 × 10−63	1.98 (1.82– 2.15)	2.79 × 10−19	1.66 (1.48– 1.86)	1.33 × 10−48	2.07 × 10−80
5p13	CAPSL a	rs1445898 (R75Q)	0.452	1.45 × 10−8	0.81 (0.76– 0.87)	0.114	0.94 (0.87– 1.01)	9.61 × 10−6	0.89 (0.84– 0.94)	0.0885	0.95 (0.88– 1.02)	0.0379	8.11 × 10−6
2q24	IFIH1	rs1990760 (A946T)	0.398	2.28 × 10−7	0.82 (0.77– 0.89)	3.84 × 10−3	0.89 (0.83– 0.89)	3.27 × 10−9	0.85 (0.81– 0.90)	4.66 × 10−4	0.88 (0.81– 0.95)	1.34 × 10−5	1.77 × 10−11
20q13	C20orf168 d	rs380421e	0.387	8.84 × 10−7	0.83 (0.78– 0.90)	0.738	0.99 (0.91– 1.07)	8.25 × 10−4	0.91 (0.87– 0.96)	7.76 × 10−3	0.91 (0.84– 0.99)	0.0554	3.99 × 10−5
20q13	SPINT4 d	rs6017667 (G73S)	0.386	1.78 × 10−6	0.84 (0.78– 0.90)	N/A
18q22	CD226	rs763361 (S307G)	0.465	2.16 × 10−5	1.17 (1.09– 1.25)	1.55 × 10−5	1.18 (1.10– 1.27)	2.82 × 10−8	1.16 (1.10– 1.22)	0.0281	1.08 (1.00– 1.16)	9.46 × 10−6	1.38 × 10−8
5p13	IL7R a	rs3194051 (I356V)	0.249	1.08 × 10−4	1.17 (1.08– 1.27)	0.0199	1.11 (1.02– 1.21)	2.06 × 10−4	1.12 (1.05– 1.19)	N/A
19p13	PDE4A	rs1051738 (A497E)	0.196	1.51 × 10−4	0.84 (0.76– 0.92)	0.603	0.97 (0.88– 1.07)	3.55 × 10−3	0.91 (0.85– 0.97)	N/A
1p32	ZMYM4 c	rs12094543e	0.0122	1.92 × 10−4	1.84 (1.32– 2.55)	0.988	1.00 (0.75– 1.32)	0.0132	1.27(1.05– 1.55)	N/A
7q31	CFTR	rs213950 (V470M)	0.396	2.18 × 10−4	1.14 (1.06– 1.23)	0.0601	1.08 (1.00– 1.16)	6.93 × 10−4	1.09 (1.04– 1.15)	4.27 × 10−3	1.11 (1.03– 1.20)	1.49 × 10−3	1.95 × 10−5
5p13	IL7Ra,c	rs6897932 (T244I)	0.285	2.19 × 10−4	0.81 (0.72– 0.91)	0.0959	0.93 (0.85– 1.01)	8.07 × 10−5	0.89 (0.84– 0.94)	0.0139	0.91 (0.84– 0.99)	6.54 × 10−3	7.77 × 10−6
3q25	MED12L	rs3732765 (R1210Q)	0.378	2.87 × 10−4	0.87 (0.81– 0.94)	0.298	0.96 (0.89– 1.04)	1.26 × 10−3	0.92 (0.87– 0.97)	N/A
20q11	LBP c	rs2232613 (L333P)	0.0917	4.43 × 10−4	0.77 (0.67– 0.89)	0.738	0.98 (0.85– 1.12)	0.0164	0.89 (0.81– 0.98)	N/A
16q23	WWOX c	rs7499843e	0.303	6.33 × 10−4	1.16 (1.07– 1.27)	0.497	1.03 (0.95– 1.11)	0.0354	1.06 (1.00– 1.12)	N/A

The genotyping of 13,378 nsSNPs, which was every possible nsSNP sequence across the entire genome to which a genotyping assay could be designed for, was carried out using molecular inversion probe technology⁸,³⁰, resulting in 7,446 nsSNPs with a MAF > 0.01 scored successfully²⁷ Chr = chromosome; MAF = minor allele frequency in control samples; N/A = not attempted; OR = odds ratio for minor allele; 95% c.i. = 95% confidence intervals; RR = relative risk for minor allele .

^aD′ = 0.99 and r² = 0.13 between IL7R SNPs rs3194051 and rs6897932. CAPSL nsSNP rs1445898 is in the same region of LD as the IL7R nsSNPs and D′ = 0.81 and r² = 0.23 and D′ = 0.95 and r² = 0.43 between rs1445898 and IL7R SNPs rs3194051 and rs6897932, respectively.

IL7R is also called CD127. IL7R nsSNP rs6897932 is in the transmembrane domain and has been associated previously with multiple sclerosis (Supplementary Note).

^bTDT P values are based on one-tailed tests (that is, the null hypothesis was not rejected unless the effect was in the same direction as the original study).

^cDifferent numbers of samples were genotyped in the GWA study for rs12094543 (ZMYM4), rs2232613 (LBP) and rs7499843 (WWOX, 2,641 affected individual and 2,484 control samples) and rs6897932 (IL7R, 1,712 affected individual and 1,529 control samples).

^dD′ = 1.00 and r² = 0.99 between rs380421 (C20orf168) and rs6017667 (SPINT47), so only rs380421 was followed up.

^eThese SNPs are no longer nsSNPs according to dbSNP build 36.