Using the independent UKB validation set, we next quantified the risk prediction performance of the metaGRS, and evaluated its association with IS via survival analysis. The metaGRS was associated with IS with a hazard ratio (HR) of 1.26 (95% CI 1.22–1.31) per standard deviation of metaGRS, which was stronger than any individual GRS comprising the metaGRS (including the IS GRS [HR = 1.18, 95% CI 1.15–1.22]) and was twice the effect size of the previously published 90-SNP IS score24 (HR = 1.13 [95% CI 1.10–1.17]; Supplementary Fig. 3a). The metaGRS also increased the C-index by 0.029 over the 90-SNP GRS (Supplementary Fig. 3b). We also assessed the performance of the IS metaGRS for predicting the AS outcome. We found the associations were consistently weaker for AS than for IS, however, as with IS, the metaGRS was a stronger predictor of AS than the 90-SNP GRS score (Supplementary Fig. 3).
