We genotyped 92 patients with stroke caused by large-vessel disease (LVD stroke) and 184 matched controls; 103 patients with stroke caused by small-vessel disease (SVD stroke) and 206 controls; and 182 patients with cardioembolic stroke (CE stroke) and 182 controls (TOAST criteria).
Plasma levels of tPA and PAI-1 antigen at follow-up were independently associated with overall ischemic stroke. tPA-antigen differed by stroke subtype and was highest among those with large-vessel disease and cardioembolic stroke.
Plasma levels of tPA and PAI-1 antigen at follow-up were independently associated with overall ischemic stroke. tPA-antigen differed by stroke subtype and was highest among those with large-vessel disease and cardioembolic stroke.
Genetic variation in the CRP gene is associated with microangiopathic but not macroangiopathic or cardioembolic stroke in a large German stroke sample.
In contrast, 3 loci from related cardiovascular GWAS studies were significant: PHACTR1 in large-vessel disease (P=2.63e(-6)), PITX2 in cardioembolic stroke (P=4.78e(-8)), and ZFHX3 in cardioembolic stroke (P=5.50e(-7)).
We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10(-16)) and ZFHX3 (p=2·28×10(-8)), and for large-vessel stroke at a 9p21 locus (p=3·32×10(-5)) and HDAC9 (p=2·03×10(-12)).
We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10(-16)) and ZFHX3 (p=2·28×10(-8)), and for large-vessel stroke at a 9p21 locus (p=3·32×10(-5)) and HDAC9 (p=2·03×10(-12)).
In contrast, 3 loci from related cardiovascular GWAS studies were significant: PHACTR1 in large-vessel disease (P=2.63e(-6)), PITX2 in cardioembolic stroke (P=4.78e(-8)), and ZFHX3 in cardioembolic stroke (P=5.50e(-7)).
We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10(-16)) and ZFHX3 (p=2·28×10(-8)), and for large-vessel stroke at a 9p21 locus (p=3·32×10(-5)) and HDAC9 (p=2·03×10(-12)).
In contrast, 3 loci from related cardiovascular GWAS studies were significant: PHACTR1 in large-vessel disease (P=2.63e(-6)), PITX2 in cardioembolic stroke (P=4.78e(-8)), and ZFHX3 in cardioembolic stroke (P=5.50e(-7)).
However, in logistic analysis for Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of ischemic stroke, nonsynonymous rs5065 (rs5065" genes_norm="4878">STOP152Arg) and rs5067 in 3'UTR of NPPA, which were in complete linkage disequilibrium, showed significant associations with cardioembolic stroke.
Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke).
Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke).
Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26 × 10<sup>-19</sup>; joint OR 1·37, 1·30-1·45, p=2·79 × 10<sup>-32</sup>) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93 × 10<sup>-7</sup>; joint OR 1·17, 1·11-1·23, p=2·29 × 10<sup>-10</sup>) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50 × 10<sup>-8</sup>; joint OR 1·24, 1·15-1·33, p=4·52 × 10<sup>-9</sup>) for large artery atherosclerosis stroke.
However, previously reported associations for the PITX2 and ZFHX3 gene loci with cardioembolic stroke subtype were replicated (P = 7 × 10<sup>-15</sup> and 6 × 10<sup>-3</sup> ).
We showed genome-wide significance for 4 loci: ABO for all IS, HDAC9 for large vessel disease (LVD), and both PITX2 and ZFHX3 for cardioembolic stroke (CE).
Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26 × 10<sup>-19</sup>; joint OR 1·37, 1·30-1·45, p=2·79 × 10<sup>-32</sup>) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93 × 10<sup>-7</sup>; joint OR 1·17, 1·11-1·23, p=2·29 × 10<sup>-10</sup>) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50 × 10<sup>-8</sup>; joint OR 1·24, 1·15-1·33, p=4·52 × 10<sup>-9</sup>) for large artery atherosclerosis stroke.