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Ligand C1 C2 B Bw4 B Bw4-80I (subset of B Bw4) Alleles considered *01, *03, *07, *08, *12, *13, *14, *16 *02, *04, *05, *06, *15, *1602, *17 *13, *27, *37, *38, *44, *47, *49, *51, *52, *53, *57, *58 *49. *51, *52, *53, *57, *58 Allele exclusions Populations not subtyped for *1602 (C2) were ommited from analysis. *13, *18w are rare and not included in analysis Rare Bw4 alleles not included: *59, *0802, *1513, *1516, *1517, *1524, *1523, *1524, *1536, *1543, *1567, *1587, *1589, *1595. All are rare in Caucasians and not consistently typed for. Rare Bw4-80I alleles not included: *59, *5901, *0803, *1513, *1516, *1517, *1523, *1524, *4013, *4019, *4406, Bw4-80I alleles rarely typed for: *4418, *2702, *3801 A Bw4 (80I) *23, *24, *25, *32 Table S1: Classification of HLA Class I ligands for KIR Polymorphism of HLA-C, -B and –A produce ligands for KIR. Alleles known to form HLA-C1, -C2, HLA-B-Bw4, HLA-B-Bw4-80I, HLA-A-Bw4 (also Bw480I) ligands for KIR are listed above. Alleles known to form KIR ligands but which are rare in Caucasians and/or not routinely typed for were ommited from analysis as indicated. HLA Ligand C1 C2 B-Bw4 B Bw4-80I North (n=97) (frequency) 0.6598 (128) 0.3402 (67) 0.3557 (69) 0.1443 (28) South (n=135) (frequency) Chi Square P value 0.6838 (186) 0.3162 (87) 0.3444 (93) 0.1185 (32) 0.2975 0.3413 0.0626 0.6680 0.8618 0.8431 0.9692 0.7161 Table S2: Frequency of HLA-Class I ligands in the North and Republic of Ireland Supplementary Figure legends Supplementary Figure S1 Higher frequency of A genotype KIR genes in Northern Europe. Synthetic maps of Europe showing 2DL3 and AA genotype carrier frequencies (%) are on the left hand side in panels A and B respectively. Geographical coordinates of populations (n=23 for 2DL3 and n=13 for AA gentoypes) are represented by points. The centre figure of each panel shows the Moran’s I values for the respective gene/genotype against distance in kilometers (km) and the right-hand figure shows 2D spatial autocorrelation values indicating the geographical direction of genetic change. The distance classes for this analysis, from the centre are 0-910km, 910-2410km and 2410-4710km for the three annuli respectively. Moran’s I values are indicated in each segment. Full segments indicate that spatial autocorrelation (p<0.05) is statistically significant, while half segments are not significant (p>0.05). Dark shading indicates varying degrees of positive spatial autocorrelation, while light shading indicates varying degrees of negative spatial autocorrelation. Supplementary Figure S2 Synthetic maps of Europe showing 3DS1 carrier and HLA-A Bw4-80I gene frequencies (%) are on the left hand side in panels A and B respectively. Geographical coordinates of populations (n=23 for 3DS1 and n=30 for HLA-A Bw4-80I) are represented by points. The centre figure of each panel shows the Moran’s I values for the respective gene/genotype against distance in kilometers (km) and the righthand figure shows 2D spatial autocorrelation values indicating the geographical direction of genetic change. The distance classes for KIR analysis, from the centre are 0-910km, 910-2410km and 24104710km for the three annuli respectively. The distance classes for HLA-B are, from the centre, 0-910, 910-2340km and 2340-4470km. Moran’s I values are indicated in each segment. Full segments indicate that spatial autocorrelation (p<0.05) is statistically significant, while half segments are not significant (p>0.05). Dark shading indicates varying degrees of positive spatial autocorrelation, while light shading indicates varying degrees of negative spatial autocorrelation.