Table 2.
Novel Genome-wide Significant Genotype-Immune Phenotype Associations
| Chr | Pos | rsID | EA | NEA | EAF | BETA (SE) | % var | INFO | n | p value | Trait | Gene | Annotation |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 82196322 | rs9324185 | C | T | 0.37 | 0.36 (0.06) | 6.22 | 0.98 | 474 | 3.51 × 10−8 | IL-6 | ADGRL2 | G |
| 1 | 198665917 | rs17612648 | G | C | 0.02 | −2.04 (0.26) | 15.70 | 0.883 | 362 | 6.22 × 10−15 | CD4+ EM | PTPRC | Co, Q, G, L |
| 1 | 198665917 | rs17612648 | G | C | 0.02 | −1.76 (0.27) | 11.84 | 0.859 | 362 | 8.94 × 10−11 | CD4+ CM | PTPRC | Co, Q, G, L |
| 1 | 198830942 | rs113116201 | C | T | 0.02 | 1.72 (0.29) | 12.26 | 0.996 | 255 | 7.58 × 10−9 | CD4+ EMRA | PTPRC | Co, Q, L |
| 1 | 198830942 | rs113116201 | C | T | 0.02 | −2.17 (0.27) | 20.08 | 0.996 | 248 | 7.52 × 10−14 | CD8+ EM | PTPRC | Co, Q, L |
| 4 | 128924522 | rs373482106 | C | CA | 0.23 | 0.49 (0.08) | 8.21 | 0.919 | 449 | 4.90 × 10−10 | KREC | LARP1B | Q, L, E |
| 5 | 38974929 | rs16867919 | G | A | 0.21 | 0.43 (0.08) | 6.13 | 1 | 475 | 3.56 × 10−8 | Th2 | RICTOR | R, G, L |
| 5 | 115413042 | rs6886944 | T | C | 0.67 | −0.54 (0.10) | 11.57 | 0.966 | 248 | 4.83 × 10−8 | CD8+ CM | COMMD10 | Co, Q, Cs, N, L |
| 7 | 21115110 | rs917812 | G | C | 0.22 | −0.46 (0.08) | 6.87 | 0.967 | 468 | 5.86 × 10−9 | Memory B | SP4 | Cs, L, E |
| 14 | 82778603 | rs1457990 | A | G | 0.51 | −0.36 (0.06) | 6.56 | 0.998 | 466 | 1.91 × 10−8 | Th17 | STON2 | Cs, L, E |
| 19 | 39745146 | rs10853728 | G | C | 0.67 | −0.48 (0.08) | 9.95 | 1 | 294 | 2.89 × 10−8 | proliferating Treg | IFNλ cluster | N, L |
Variants associated with p < 5 × 10−8. SNPs rs17612648 and rs113116201 at the PTPRC locus are in LD (r2 = 0.62 in EURs, r2 = 1 in CEU) and conditional analyses were not able to distinguish between them (see also Table S3). Annotation indicates whether the variant is or is in LD with (r2 > 0.8) a coding variant (Co) or known splicing or expression quantitative trait locus (Q) or is conserved (Cs), whether the variant disrupts a regulatory motif (R), whether the variant is located in the candidate gene (G) or the candidate gene is the nearest gene to the variant (N), and whether the candidate gene is supported by biological evidence in the literature (L) or by expression data obtained in this study (E). For all three regions where both trait and variant have appropriate equivalents in previous GWASs, our findings replicated with nominal significance (p < 0.05) or showed a trend in the same direction (see also Table S2). BETA, effect; Chr, chromosome; EA, effect allele; EAF, effect allele frequency; INFO, imputation quality, with 1 for directly genotyped variants; n, number of individuals with genotype and immune phenotype; NEA, non-effect allele; Pos, position in GRCh37; rsID, reference SNP identification; SE, standard error; % var, percentage of variance explained.