Seven top SNPs and their associations with annualised change in disability (ΔEDSS)*
| ΔEDSS | ||||
|---|---|---|---|---|
| SNP | Chromosome | Gene† | Number of 5-year disability measures (%) | β (95% CI) |
| rs7588193‡ | 2 | ZFP36L2, HAAO | ||
| AA | 74 (59.20) | 0.27 (0.22 to 0.32) | ||
| AG§+GG§ | 51 (40.80) | +0.12 (0.04 to 0.21) | ||
| Trend | p=0.005 | |||
| rs842639¶ | 2 | FLJ16341 | ||
| GG | 16 (12.80) | 0.16 (0.05 to 0.26) | ||
| AG | 48 (38.40) | +0.17 (0.04 to 0.29) | ||
| AA§ | 61 (48.80) | +0.20 (0.08 to 0.32) | ||
| Trend | p=0.007 | |||
| rs35967351¶ | 1 | SLAMF7 | ||
| TT+AT | 65 (52.00) | 0.26 (0.21 to 0.32) | ||
| AA§ | 60 (48.00) | +0.11 (0.03 to 0.19) | ||
| Trend | p=0.010 | |||
| rs2283792¶ | 22 | MAPK1 | ||
| AA | 34 (27.20) | 0.26 (0.19 to 0.34) | ||
| CA | 64 (51.20) | +0.04 (−0.06 to 0.14) | ||
| CC§ | 27 (21.60) | +0.17 (0.04 to 0.29) | ||
| Trend | p=0.013 | |||
| rs3825568 | 14 | ZFP36L1 | ||
| GG | 33 (27.05) | 0.26 (0.18 to 0.34) | ||
| GA§ | 59 (48.36) | +0.06 (−0.04 to 0.16) | ||
| AA§ | 30 (24.59) | +0.15 (0.03 to 0.27) | ||
| Trend | p=0.016 | |||
| rs2546890 | 5 | LOC285626 | ||
| AA | 46 (36.80) | 0.26 (0.19 to 0.32) | ||
| AG§ | 52 (41.60) | +0.09 (−0.01 to 0.19) | ||
| GG§ | 27 (21.60) | +0.12 (0.01 to 0.24) | ||
| Trend | p=0.030 | |||
| rs8070345 | 17 | VMP1 | ||
| GG | 32 (25.60) | 0.26 (0.18 to 0.34) | ||
| GA§ | 61 (48.80) | +0.06 (−0.05 to 0.16) | ||
| AA§ | 32 (25.60) | +0.12 (0.0009 to 0.24) | ||
| Trend | p=0.047 | |||
Disability results presented as geometric mean ΔEDSS (95% CI) for the reference group, while coefficients relative to reference (β (95% CI)) are presented for subsequent levels.
Results in boldface denote statistically significant results (p<0.05).
*Adjusted for age, sex, study recruitment centre and whether participants were having a relapse at the time of their 5-year disability measurement, before adjustment for multiple comparisons.
†Provide nearest two genes for intergenic SNPs.
‡The homozygous genotypes were combined with the heterozygous ones due to small numbers.
§Risk genotype for CGRS.
¶For consistency, non-risk alleles was always set as reference. ΔEDSS, annualised disability progression from FDE to 5-year review; CGRS, cumulative genetic risk score; EDSS, Expanded Disability Status Scale; FDE, first demyelinating event; MS, clinically definite multiple sclerosis; SNPs, single nucleotide polymorphisms.