HTRA1 and ischemic stroke: Consistent with distinct effects of R227W in the coronary circulation versus the cerebrovasculature: carriers of R227W had a significantly increased risk of coronary artery disease (OR [CAD], 1.46 [95% CI, 1.00–2.13]; P=0.049) and acute MI (OR [MI]; 2.32 [95% CI, 1.30–4.19]; P=0.005) compared with other carriers of predicted damaging missense variants in HTRA1 (minor allele frequency <0.001; Rare Exome Variant Ensemble Learner score >0.5) but reduced risk of ischemic stroke (OR [ischemic stroke], 0.43 [95% CI, 0.18–0.93]; P=0.04; Figure 4G).