and 9p21 loci, the associations were replicated in the independent METASTROKE samples (table 2). The population attributable risks in the METASTROKE discovery cohort were estimated as 5·8% for PITX2 and 7·0% for ZFHX3 in cardioembolic stroke, and 4·5% for HDAC9 and 7·2% for 9p21 in large-vessel disease.Table 2METASTROKE association signals for SNPs identified in previous genome-wide association studies by gene and disease subtypeChrBPSNPRARAFFull METASTROKE discovery sampleExcluding cohorts used in previous discovery of relevant association*OR (95% CI)p value†OR (95% CI)p value†HDAC9719 015 913rs2107595A0·16IS..........1·12 (1·07–1·17)4·34×10−61·11 (1·05–1·17)7·8×10−5LVD..........1·39 (1·27–1·53)2·03×10−161·39 (1·24–1·56)3·15×10−8SVD..........1·03 (0·93–1·14)0·571·11 (0·96–1·29)0·92CE..........1·07 (0·98–1·17)0·151·07 (0·96–1·19)0·25PITX24111 937 516rs6843082G0·21IS..........1·11 (1·06–1·15)1·95×10−71·09 (1·04–1·14)1·12×10−4LVD..........1·06 (0·97–1·15)0·171·03 (0·93–1·13)0·61SVD..........1·04 (0·96–1·14)0·311·01 (0·90–1·13)0·91CE..........1·36 (1·27–1·47)2·8×10−161·32 (1·23–1·44)3·64×10−12ZFHX31671 626 169rs879324A0·19IS..........1·05 (1·00–1·09)0·0371·06 (1·01–1·11)0·021LVD..........1·06 (0·98–1·16)0·151·06 (0·96–1·17)0·32SVD..........0·99 (0·91–1·09)0·941·01 (0·91–1·13)0·81CE..........1·25 (1·15–1·35)2·28×10−81·25 (1·15–1·36)1·53×10−7NINJ212645 460rs11833579A0·22IS..........1·06 (1·02–1·10)6·1×10−41·00 (0.96–1·05)0·81LVD..........0·99 (0·91–1·08)0·870·99 (0·91–1·08)0·79SVD..........0·98 (0·90–1·08)0·790·99 (0·90–1·08)0·79CE..........1·04 (0·97–1·13)0·271·00 (0·92–1·09)0·959p21922 105 959rs2383207G0·52IS..........1·04 (0·76–1·41)0·0241·03 (0·99–1·07)0·16LVD..........1·15 (1·08–1·23)3·32×10−51·15 (1·04–1·27)5·69×10−3SVD..........1·02 (0·96–1·10)0·481·03 (0·93–1·14)0·61CE..........0·96 (0·91–1·03)0·241·02 (0·92–1·14)0·61PRKCHIS1461 077 900rs2246700A0·841·07 (1·02–1·12)0·0049....LVD1460 894 555rs12587610G0·311·11 (1·03–1·21)0·0046....SVD1461 114 037rs2255146G0·821·22 (1·03–1·43)0·0175....CE1460 988 886rs3825655C0·951·31 (1·00–1·71)0·0475....Chr=chromosome. BP=base position. SNP=single nucleotide polymorphism. RA=risk allele. RAF=risk allele frequency. OR=odds ratio. IS=all ischaemic strokes. LVD=large vessel disease. SVD=small vessel disease. CE=cardioembolic stroke.*Statistics shown are after removal of discovery populations showing an association between the gene and stroke from original publications—ie, deCODE excluded for PITX2, ZFHX3;8, 9 WTCCC2-UK and WTCCC-Munich excluded for HDAC9;14 WTCCC2-UK and WTCCC2-Munich, ISGS/SWISS, GEOS, and
