Table 3. Common a2-, a6-, or a14-containing (or other) extended haplotypes††.
| HLA Haplotype | |||||||
|---|---|---|---|---|---|---|---|
| Name† | A~C~B~DRB1~DQB1~SNP | Frequency | OR* | p-value** | |||
| c23 | 30:02~05:01~18:01~03:01~02:01~a2 | 212 | 2.0 (1.4–2.7) | < E-4 | |||
| c46 | 01:01~07:01~08:01~03:01~02:01~a2 | 128 | 2.1 (1.5–3.0) | < E-4 | |||
| c85 | 02:01~05:01~18:01~03:01~02:01~a2 | 75 | 1.7 (1.0–2.9) | < 0.05 | |||
| c1§ | 01:01~07:01~08:01~03:01~02:01~a6 | 3782 | 1.1 (1.0–1.2) | < 0.05 | |||
| c14 | 02:01~07:01~08:01~03:01~02:01~a6 | 397 | 0.9 (0.7–1.2) | ns | |||
| c27 | 03:01~07:01~08:01~03:01~02:01~a6 | 181 | 1.7 (1.2–2.3) | < E-2 | |||
| c51 | 68:01~07:01~08:01~03:01~02:01~a6 | 121 | 0.6 (0.4–1.0) | < 0.05 | |||
| c68 | 24:02~07:01~08:01~03:01~02:01~a6 | 91 | 3.0 (1.8–4.9) | < E-5 | |||
| c90 | 03:01~07:02~07:02~03:01~02:01~a6 | 71 | 1.6 (0.9–2.6) | ns | |||
| c97 | 32:01~07:01~08:01~03:01~02:01~a6 | 68 | 1.1 (0.6–2.0) | ns | |||
| c110 | 25:01~07:01~08:01~03:01~02:01~a6 | 63 | 1.3 (0.7–2.3) | ns | |||
| c34 | 68:02~08:02~14:02~13:03~03:01~a14 | 161 | 1.9 (1.3–2.8) | < E-3 | |||
| c96 | 66:01~17:01~41:02~13:03~03:01~a14 | 69 | 2.6 (1.5–4.5) | < E-3 | |||
| c107 | 02:01~17:01~41:02~13:03~03:01~a14 | 64 | 1.9 (1.1–3.4) | < 0.05 | |||
| c5§§ | 02:01~05:01~44:02~04:01~03:01~a3 | 906 | 0.5 (0.4–0.6) | < E-11 | |||
| c15 | 02:01~06:02~13:02~07:01~02:02~a3 | 361 | 0.5 (0.3–0.6) | < E-5 | |||
| c18 | 02:01~06:02~57:01~07:01~03:03~a5 | 293 | 0.5 (0.3–0.7) | < E-4 | |||
| c24 | 02:01~01:02~27:05~01:01~05:01~a9 | 211 | 0.5 (0.3–0.7) | < E-3 | |||
| c30 | 02:01~05:01~44:02~11:01~03:01~a4 | 173 | 0.6 (0.4–0.9) | < 0.05 | |||
| c32 | 03:01~07:02~07:02~13:01~06:03~a18 | 166 | 0.6 (0.4–0.9) | < E-2 | |||
| c73 | 02:01~15:02~51:01~09:01~03:03~a4 | 87 | 0.4 (0.2–0.8) | < E-2 | |||
| c81 | 24:02~07:02~39:06~08:01~04:02~a16 | 79 | 3.1 (1.8–5.5) | < E-4 | |||
†† haplotypes with ≥ 50 representations in the WTCCC. All such haplotypes carrying the a2, a6, or a14 SNP haplotype are included. For each of the listed haplotypes, the Class I and Class II portions were significantly associated with each other far beyond the Bonferroni-adjusted level of significance.
† Arbitrary name for haplotype (sorted in descending order of frequency) for the entire WTCCC population.
* Odds ratio (OR) of disease for individuals having 1 copy of the listed haplotype compared to having no copies of the particular HLA-DRB1~HLA-DQB1~SNP Class II haplotype (95% CI range in parenthesis). All haplotypes carrying the HLA-DRB1*15:01~HLA-DQB1*06:02~a1 Class II motif were excluded in this analysis. A Bonferroni correction for the number of haplotypes with 50 or more representations (146) would require a significance level of (p<3*E-4).
** Significance of the association between having 1 copy of the specific allele and the disease (MS) compared to having no copies. The p-values are expressed in scientific notation as powers of 10 (E); ns = not significant. With exception of c23 and c46, all observations with p<0.001 still showed a statistically significant effect even after adjustment for population stratification, geographic, stratification, and gender. Moreover, even c23 and c46 trended in this direction (p≈0.10)
§ Only the c1 haplotype had enough observations to explore the disease association for having two copies of an allele compared to having no copies of the HLA-DRB1*03:01~HLA-DQB1*02:01~a6 Class II haplotype. Thus, this OR was
For c1: OR [two copies] = 2.1 (1.5–2.9); p = 2.1*E-6
This effect was still statistically significant even after adjustment for population stratification (p = 3.13*E-6).
The other Class II haplotypes containing HLA-DRB1*03:01~HLA-DQB1*02:01~a6, combined, had an OR of:
OR [two copies] = 0.8 (0.1–3.4); p = ns
§§ This group of haplotypes is composed of those that also had a significant association with this disease. Most of these haplotypes seem to be protective and this protective effect remained significant (p<0.05) even after excluding all individuals who carried the HLA-DRB1*15:01~HLA-DQB1*06:02~a1 haplotype.