Table 2.
MEGASTROKE stroke-significant loci replicated using UKB stroke definitions.
| Known stroke genetic locus | Significantly associated stroke type in MEGASTROKE | MEGASTROKE European meta-analyses N = 40,585* | MEGASTROKE transethnic meta-analyses N = 67,162† | Stroke-specific code from any medical setting N = 8,665 | Broad CVD code from any medical setting N = 8,085 | Stroke-specific or Broad CVD code from any medical setting N = 16,750 | Specific or non-specific self-reported stroke event N = 7,536 | Any code or self-reported event N = 19,449 |
|---|---|---|---|---|---|---|---|---|
| CHR4: rs13143308 (PITX2) | Cardio-embolic stroke |
1.34 (1.28–1.40) 5.2 × 10−41 |
1.32 (1.27–1.37) 1.9 × 10−47 |
1.09 (1.05–1.13) 7.5 × 10−6 |
1.06 (1.02–1.1) 0.0036 |
1.08 (1.05–1.11) 1 × 10−7 |
1.04 (0.995–1.08) 0.08 |
1.07 (1.04–1.1) 3 × 10−7 |
| CHR7: rs2107595 (HDAC9–TWIST1) | Large-vessel stroke |
1.27 (1.19–1.35) 1.4 × 10−13 |
1.21 (1.15–1.26) 3.7 × 10−15 |
1.07 (1.03–1.12) 1 × 10−3 |
1.03 (0.99–1.08) 0.12 |
1.05 (1.02–1.09) 4.7 × 10−4 |
1.08 (1.03–1.13) 8.9 × 10−4 |
1.06 (1.03–1.09) 1.1 × 10−4 |
| CHR10: rs2295786 (SH3PXD2A) | All stroke | 1.05 (1.03–1.07) 1.4 × 10–7 |
1.05 (1.04–1.07) 1.8 × 10−10 |
1.07 (1.04–1.11) 1.5 × 10−5 |
1.01 (0.98–1.04) 0.59 |
1.04 (1.02–1.07) 4 × 10−4 |
1.04 (1.01–1.08) 0.021 |
1.05 (1.03–1.07) 5.1 × 10−6 |
| CHR12: rs3184504 (SH2B3) | All ischaemic stroke |
1.08 (1.06–1.10) 1.2 × 10−14 |
1.08 (1.06–1.10) 2.2 × 10−14 | 1.04 (1.01–1.07) 0.0096 |
1 (0.97–1.03) 0.83 | 1.02 (1–1.05) 0.04 |
1.06 (1.03–1.1) 1.9 × 10−4 | 1.03 (1.01–1.05) 0.0068 |
| CHR9: rs635634 (ABO) | All ischaemic stroke |
1.08 (1.05–1.11) 9.2 × 10−9 |
1.07 (1.04–1.10) 6.9 × 10–3 |
1.08 (1.03–1.12) 1.8 × 10−4 |
1 (0.96–1.04) 0.86 | 1.04 (1.01–1.07) 0.0043 |
1.1 (1.05–1.14) 5.8 × 10−6 |
1.05 (1.02–1.07) 4.3 × 10−4 |
| CHR9: rs7859727 (Chr9p21) | All stroke | 1.05 (1.03–1.07) 7.2 × 10–8 |
1.05 (1.03–1.07) 4.2 × 10−10 |
1.06 (1.03–1.09) 8.1 × 10−5 |
1.04 (1.01–1.07) 0.018 |
1.05 (1.03–1.07) 5.3 × 10−6 |
1.02 (0.98–1.05) 0.32 |
1.04 (1.02–1.06) 6.3 × 10−5 |
| Summary: number replicated loci | 5/32 | 0/32 | 4/32 | 3/32 | 5/32 | |||
Significant associations are in bold in shaded boxes. CVD, cerebrovascular disease; CHR, chromosome; N, number.
†
MEGASTROKE transethnic meta-analyses included 60,341 ischaemic stroke cases; 9,006 cardio-embolic stroke cases; 6,688 large-vessel stroke cases. MEGASTROKE European meta-analyses included 34,217 ischaemic stroke cases; 7,193 cardio-embolic stroke cases; 4,373 large-vessel stroke cases.