Supplementary Table 1:Analysis of Single SNPs across the SLAM locus by GENEHUNTER-TDT

rs number / SNP Analysed / Gene / Function / UK / Canada / UK-Canada
MA / T:U / χ2 / P
value / T/U / MA / T:U / χ2 / P value / T/U / MA / T:U / χ2 / P value / T/U
rs352692 / 2 / CD48-SLAMF7 / G / 14:20 / 1.06 / 0.304 / 0.7 / G / 111:122 / 0.519 / 0.471 / 0.91 / G / 125:142 / 1.08 / 0.298 / 0.88
rs493646 / 3 / CD48-SLAMF7 / G / 102:62 / 9.76 / 0.00180 / 1.7 / G / 92:118 / 1.28 / 0.258 / 0.78 / G / 194:172 / 1.32 / 0.250 / 1.1
rs503832 / 4 / CD48-SLAMF7 / T / 119:100 / 1.648 / 0.199 / 1.19
rs579272 / 6 / CD48-SLAMF7 / A / 118:121 / 0.0380 / 0.846 / 0.98 / A / 87:116 / 4.143 / 0.0418 / 0.75 / A / 205:237 / 2.32 / 0.128 / 0.87
rs983494 / 7 / CD48-SLAMF7 / A / 64:86 / 3.23 / 0.0724 / 0.74 / A / 90:77 / 1.012 / 0.315 / 1.17 / A / 155:163 / 0.201 / 0.654 / 0.95
rs489286 / 8 / SLAMF7 / I6 / A / 130:116 / 0.797 / 0.372 / 1.1 / A / 109:85 / 2.97 / 0.0849 / 1.3 / A / 239:201 / 3.28 / 0.0701 / 1.2
rs526030 / 9 / SLAMF7 / 3'UTR / T / 15:6 / 3.86 / 0.0495 / 2.5 / T / 13:21 / 1.88 / 0.170 / 0.62 / A / 27:28 / 0.018 / 0.893 / 0.96
rs564883 / 11 / SLAMF7-LY9 / C / 127:141 / 0.731 / 0.293 / 0.90 / T / 95:105 / 0.500 / 0.480 / 0.904 / T / 222:226 / 0.0360 / 0.850 / 0.98
rs1333065 / 12 / LY9 / I2 / G / 59:62 / 0.074 / 0.785 / 0.95 / G / 86:116 / 4.46 / 0.0348 / 0.74 / G / 145:178 / 3.37 / 0.0663 / 0.82
rs579589 / 14 / LY9 / I6 / A / 99:105 / 0.176 / 0.674 / 0.94
rs3817407 / 15 / LY9 / E8 / G / 107:89 / 1.65 / 0.199 / 1.2 / G / 61:105 / 11.66 / 6.0E-4 / 0.58 / G / 168:194 / 1.87 / 0.172 / 0.87
rs509749 / 17 / LY9 / 3'UTR / G / 145:163 / 1.05 / 0.305 / 0.89 / G / 101:134 / 4.63 / 0.0313 / 0.75 / G / 248:299 / 4.76 / 0.0292 / 0.83
rs480104 / 18 / CD244 / I1 / C / 65:87 / 3.18 / 0.0744 / 0.75 / C / 76:77 / 0.00700 / 0.936 / 0.99 / C / 144:165 / 1.43 / 0.232 / 0.87
rs2990703 / 20 / CD244 / I1 / C / 131:114 / 1.18 / 0.277 / 1.1
rs1855188 / 21 / CD244 / C / 81:80 / 0.00600 / 0.937 / 1.0
rs955370 / 22 / CD244-ITLN1 / G / 54:69 / 1.83 / 0.176 / 0.78 / G / 77:74 / 0.0600 / 0.807 / 1.0 / G / 131:145 / 0.710 / 0.399 / 0.90
rs955371 / 23 / CD244-ITLN1 / T / 80:79 / 0.00600 / 0.937 / 1.0
rs869167 / 24 / CD244-ITLN1 / A / 91:118 / 3.49 / 0.062 / 0.77 / A / 99:107 / 0.311 / 0.577 / 0.93 / A / 119:220 / 1.05 / 0.305 / 0.54
rs4656955 / 26 / ITLN1 / I7 / A / 80:118 / 7.29 / 0.00690 / 0.68 / A / 104:101 / 0.044 / 0.834 / 1.0 / A / 185:223 / 3.54 / 0.0600 / 0.83
rs3766356 / 27 / ITLN1 / I5 / T / 96:130 / 5.12 / 0.0237 / 0.74 / T / 102:99 / 0.045 / 0.832 / 1.0 / T / 199:232 / 2.53 / 0.112 / 0.86
rs2236515 / 28 / ITLN1 / I2 / T / 77:106 / 4.60 / 0.0321 / 0.73 / T / 101:99 / 0.02 / 0.888 / 1.0 / T / 179:208 / 2.17 / 0.140 / 0.86
rs2039415 / 31 / ITLN1 / T / 82:119 / 6.81 / 0.00910 / 0.69 / T / 101:99 / 0.02 / 0.888 / 1.0 / T / 184:221 / 3.38 / 0.0660 / 0.83
rs4656959 / 32 / ITLN1-ITLN2 / G / 86:120 / 5.61 / 0.0178 / 0.72 / G / 97:91 / 0.191 / 0.662 / 1.0 / G / 184:214 / 2.26 / 0.133 / 0.86
rs2225591 / 33 / ITLN1-ITLN2 / C / 79:122 / 9.20 / 0.00240 / 0.65 / - / 107:107 / 0.00 / 1.00 / 1.0 / C / 178:232 / 4.83 / 0.0279 / 0.77
rs2184064 / 34 / ITLN1-ITLN2 / A / 68:104 / 7.54 / 0.00610 / 0.65 / A / 104:100 / 0.078 / 0.779 / 1.0 / A / 173:207 / 3.04 / 0.081 / 0.84
rs7516660 / 35 / ITLN1-ITLN2 / G / 72:92 / 2.44 / 0.118 / 0.78 / - / 104:104 / 0.00 / 1.00 / 1.0 / G / 177:197 / 1.07 / 0.301 / 0.90
rs2774277 / 36 / ITLN1-ITLN2 / T / 25:55 / 11.3 / 8.0E-4 / 0.45 / T / 37:44 / 0.605 / 0.437 / 0.84 / T / 62:99 / 8.50 / 8.0E-4 / 0.63
rs6693472 / 37 / ITLN2 / E4 / G / 2:3 / 0.200 / 0.655 / 0.67 / 0.88
rs2255842 / 38 / ITLN2-F11R / G / 87:88 / 0.00600 / 0.937 / 0.67 / 1.13
rs1556260 / 39 / USF1 / I1 / A / 61:71 / 0.758 / 0.384 / 0.86
rs1556259 / 40 / USF1 / I1 / C / 62:72 / 0.746 / 0.388 / 0.86 / 0.87

TDT analysis by GENEHUNTER for each SNP tested in the UK SLE families and in the Canadian trios. A separate analysis was performed for the UK and Canadian families and also for joint UK/Canadian samples. The column marked “SNP analysed”, gives the order of analysed SNPs shownin Figure 1. For each variant the P value is quoted with one degree of freedom. The column marked “T:U” is the ratio of informative families showing transmission of the quoted minor allele to those families not showing transmission. The column marked T/U represents the normalised transmission:untransmission ratio.

Supplementary Table 2:Transmission:Untransmission Ratios between the UK and Canadian Complete Trios across the SLAM locus

SNP / SNP Analysed / UK Trios / Canadian Trios / Pearson’s Chi-Square
T:U / OR / CI / T:U / OR / CI / χ2 / P value
rs352692 / 2 / 14:20 / 0.700 / 0.429-1.14 / 111:122 / 0.910 / 0.758-1.09 / 0.873 / 0.350
rs493646 / 3 / 102:62 / 1.65 / 1.31-2.07 / 92:118 / 0.780 / 0.642-0.847 / 12.5 / 4 x 10-4
rs579272 / 6 / 118:121 / 0.980 / 0.851-1.67 / 87:116 / 0.750 / 0.615-0.915 / 1.87 / 0.171
rs983494 / 7 / 64:86 / 0.740 / 0.590-0.938 / 90:77 / 1.17 / 0.942-1.45 / 3.97 / 0.0458
rs489286 / 8 / 130:116 / 1.12 / 0.939-1.34 / 109:85 / 1.28 / 1.05-1.57 / 0.488 / 0.485
rs526030 / 9 / 15:6 / 2.50 / 1.21-5.18 / 13:21 / 0.62 / 0.375-1.02 / 6.82 / 0.00900
rs564883 / 11 / 127:141 / 0.900 / 0.761-1.07 / 95:105 / 0.900 / 0.743-1.10 / 0.00100 / 0.981
rs1333065 / 12 / 59:62 / 0.950 / 0.740-1.22 / 86:116 / 0.740 / 0.607-0.905 / 1.71 / 0.279
rs3817407 / 15 / 107:89 / 1.20 / 0.985-1.47 / 61:105 / 0.580 / 0.461-0.732 / 11.5 / 0.0006
rs509749 / 17 / 145:163 / 0.890 / 0.759-1.04 / 101:134 / 0.750 / 0.627-0.906 / 0.0418 / 0.342
rs480104 / 18 / 65:87 / 0.750 / 0.594-9.40 / 76:77 / 0.990 / 0.789-1.23 / 0.904 / 0.342
rs955370 / 22 / 54:69 / 0.780 / 0.607-1.01 / 77:74 / 1.04 / 0.830-1.30 / 1.37 / 0.243
rs869167 / 24 / 91:118 / 0.770 / 0.635-0.937 / 99:107 / 0.930 / 0.762-1.23 / 0.853 / 0.356
rs4656955 / 26 / 80:118 / 0.680 / 0.553-0.832 / 104:101 / 1.03 / 0.848-1.25 / 4.33 / 0.0374
rs3766356 / 27 / 96:130 / 0.740 / 0.612-0.892 / 102:99 / 1.03 / 0.847-1.25 / 0.0827 / 0.0872
rs2236515 / 28 / 77:106 / 0.730 / 0.589-0.896 / 101:99 / 1.02 / 0.839-1.24 / 2.73 / 0.0987
rs2039415 / 31 / 82:119 / 0.690 / 0.563-0.844 / 101:99 / 1.02 / 0.839-1.24 / 0.0974 / 0.0510
rs4656959 / 32 / 86:120 / 0.720 / 0.588-0.874 / 97:91 / 1.07 / 0.871-1.31 / 3.83 / 0.0502
rs2225591 / 33 / 79:122 / 0.650 / 0.528-0.795 / 107:107 / 1.00 / 0.827-1.21 / 4.80 / 0.0285
rs2184064 / 34 / 68:104 / 0.650 / 0.524-0.815 / 104:100 / 1.04 / 0.857-1.26 / 4.93 / 0.0264
rs7516660 / 35 / 72:92 / 0.780 / 0.628-0.975 / 104:104 / 1.00 / 0.825-1.21 / 1.37 / 0.242
rs2774277 / 36 / 25:55 / 0.450 / 0.318-0.650 / 37:44 / 0.840 / 0.617-1.15 / 3.54 / 0.0599

Pearson’s Chi-Square analysis was used to test for differences in the T:U ratios in the UK and Canadian complete trios, with a threshold of P = 0.001 for a significant difference. The column marked “SNP analysed”, gives the order of analysed SNPs. For each variant in both populations the Odds Ratios (OR) and 95% Confidence Intervals (CI) are given.

Supplementary Table 3:Conditional Analysis of the Association in LY9

Conditioning by SNP
Conditioning SNP / SNP Analysed / LRT / df / P value
Global / 10.228 / 5 / 0.069
rs1333065 / 12 / 5.648 / 4 / 0.227
rs3817407 / 15 / 5.132 / 4 / 0.274
rs509749 / 17 / 2.193 / 4 / 0.700
rs480104 / 18 / 8.912 / 4 / 0.063

Conditional analysis of variants in LY9 in the UK and Canadian SLE populations using WHAP. The analysis was performed on a cohort of 732 parental-proband trios (461 UK and 271 Canadian families). The column marked “SNP analysed”, gives the number of the analysed SNPs shown in Table 2. The omnibus test gives the global association for the SNPs across LY9 shown in the table. Each constituent variant was used to condition (control) the global association and the results for each variant are presented as a log-likelihood ratio (LRT), with the degrees of freedom (df) and the P value.

Region / SNPs analysed / SNP location / Omnibus Test / Conditional Analysis
LRT / df / P value / Conditioning SNP / LRT / df / P value
A / SLAMF7-LY9 / Omnibus
rs1333065
rs3817407
rs509749
rs480104 / SLAMF7-LY9
LY9
LY9
LY9 / 15.095 / 9 / 0.0840 / rs2039415 / 8.651 / 8 / 0.373
Conditioning SNP / rs4656959 / ITLN1-ITLN2
B / ITLN1-ITLN2 / Omnibus
rs4656955
rs2039415
rs4656959
rs2225591
rs2184064 / ITLN1
ITLN1
ITLN1-ITLN2
ITLN1-ITLN2
ITLN1-ITLN2 / 11.120 / 4 / 0.0253 / rs509749 / 3.104 / 3 / 0.376
Conditioning SNP / rs509749 / LY9

Supplementary Table 4:Conditional Analysis of LY9 and the Intelectin Genes in UK SLE Families.

Conditional analysis of variants in LY9 in the UK and Canadian SLE populations using WHAP. The analysis was performed on a cohort of 461 UK parental-proband trios. The column marked “SNP location” gives the location of the SNPs within the SLAM gene cluster. For each analysis, the results are presented as a log-likelihood ratio (LRT) with degrees of freedom (df) and P value. A) Conditional analysis of the SNPs in the SLAMF7-LY9 region with the SNP showing the strongest association in the ITLN1-ITLN2 region. The column marked “Omnibus Test” shows the association of the SNPs in the SLAMF7-LY9 region and including the conditioning variant, rs2039415 in the ITLN1-ITLN2 intergenic region. B) Conditional analysis of the SNPs in the ITLN1-ITLN2 region with rs509749, the non-synonymous SNP in LY9. The column marked “Omnibus Test” shows the association of the SNPs in the ITLN1-ITLN2 region and including the SNP used for the conditional analysis, rs509749 in LY9.