Table 4.
Gender and HLA-DRB1 contributes to the MSGB in Probands, absence of reverse aggregation of Non-MHC-SNPs
| MSGB Component Distribution | rs3135388 (T, T) HLA-DRB1*15:01 Double dose | rs3135388 (T, C) HLA-DRB1*15:01 Single dose | rs3135388 (C, C) HLA-DRB1*15:01 Negative | Cuzick’s Test P-value | Unrelated Controls (n=250) | |||
|---|---|---|---|---|---|---|---|---|
| P50 (P25-P75) | Female (n=86) | Male (n=22) | Female (n=439) | Male (n=115) | Female (n=393) | Male (n=156) | ||
|
| ||||||||
| Gender+ HLA+ non-MHC SNPs | 5.96 (5.71–6.29) | 5.31 (5.10–5.71) | 4.97 (4.70–5.21) | 4.48 (4.26–4.66) | 3.92 (3.68–4.18) | 3.50 (3.31–3.73) | z=30.2 p<10−16 |
3.65 (3.28–4.06) |
|
| ||||||||
| HLA + non-MHC SNPs | 5.49 (5.24–5.82) | 5.31 (5.10–5.71) | 4.50 (4.23–4.74) | 4.48 (4.26–4.66) | 3.45 (3.21–3.71) | 3.50 (3.31–3.73) | z=21.0 p<10−16 |
3.50 (3.18–3.89) |
|
| ||||||||
| Gender + non-MHC SNPs | 3.93 (3.68–4.27) | 3.28 (3.07–3.69) | 3.96 (3.69–4.20) | 3.47 (3.25–3.65) | 3.92 (3.68–4.18) | 3.50 (3.31–3.73) | z=6.0 p=2.4e-09 |
3.45 (3.18–3.76) |
|
| ||||||||
| Non-MHC SNPs only | 3.46 (3.21–3.80) | 3.28 (3.07–3.69) | 3.49 (3.22–3.73) | 3.47 (3.25–3.65) | 3.45 (3.21–3.71) | 3.50 (3.31–3.73) | z=0.45 p=0.65 |
3.36 (3.12–3.62) |
Table 4 presents medians and inter-quartile ranges (P25-P75) of the Multiple Sclerosis Genetic Burden (MSGB) in probands of multi-case and sporadic MS families grouped according to HLA-DRB1*15:01 dose (rs3135388*T) and gender, and controls. P-values correspond to two-sided Cuzick’s test of the MSGB gradient. MSGB is computed using the components indicated at the beginning of each row: gender, HLA (the HLA-DRB1*15:01 component in the MHC region), and non MHC-SNPs components.