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. Author manuscript; available in PMC: 2017 Jun 1.
Published in final edited form as: Lancet Neurol. 2016 Apr 7;15(7):695–707. doi: 10.1016/S1474-4422(16)00102-2

Table 3.

Validation of top loci in independent cross-sectional case-control studies associated with risk of stroke

Gene Discovery
Validation
Combined total
CHARGE
SiGN
METASTROKE
HVH1
CADISP
Validation
meta-analysis
Meta-analysis
Hazard
ratio
(95% CI)		 p value Odds
ratio
(95% CI)		 p value Odds
ratio
(95% CI)		 p value Odds
ratio
(95% CI)		 p value Odds
ratio
(95% CI)		 p value Odds
ratio
(95% CI)		 p value Odds
ratio
(95% CI)		 p value
All stroke*
rs6433905 UBE2E3 1·21 (1·12–1·31) 2·54 × 10−6 1·02 (0·97–1·08) 0·41 1·11 (0·98–1·27) 0·11 1·09 (0·83–1·44) 0·54 0·72 (0·54–0·95) 0·018 1·03 (0·98–1·07) 0·22 1·07 (1·03–1·12) 8·72 × 10−4
rs12204590† FOXF2 1·14 (1·08–1·20) 2·17 × 10−6 1·07 (1·03–1·11) 1·02 × 10−3 1·07 (0·98–1·16) 0·13 1·03 (0·86–1·24) 0·73 1·08 (0·92–1·26) 0·36 1·06 (1·03–1·09) 2·15 × 10−4 1·08 (1·05–1·12) 1·48 × 10−8
rs790919 OPRM1 1·12 (1·07–1·17) 2·44 × 10−6 1·00 (0·97–1·03) 0·88 1·01 (0·95–1·09) 0·70 0·88 (0·76–1·02) 0·10 1·06 (0·93–1·21) 0·37 1·00 (0·98–1·03) 0·80 1·03 (1·01–1·05) 0·013
rs11788316 FLJ41200 1·13 (1·07–1·19) 2·49 × 10−6 0·99 (0·96–1·03) 0·73 1·07 (0·99–1·16) 0·074 1·01 (0·84–1·21) 0·93 0·99 (0·85–1·15) 0·89 1·01 (0·99–1·04) 0·38 1·03 (1·01–1·06) 7·53 × 10−3
rs11627959 CFL2 0·89 (0·85–0·93) 2·23 × 10−6 0·99 (0·96–1·02) 0·70 1·00 (0·93–1·08) 0·93 1·00 (0·85–1·17) 0·96 1·03 (0·90–1·18) 0·62 1·01 (0·98–1·03) 0·53 0·97 (0·95–0·99) 0·011
rs4899120 SYNE2 1·19 (1·11–1·29) 4·71 × 10−6 1·02 (0·97–1·07) 0·50 1·00 (0·88–1·14) 0·98 1·05 (0·80–1·37) 0·73 1·16 (0·92–1·46) 0·21 1·02 (0·99–1·07) 0·23 1·06 (1·02–1·10) 2·00 × 10−3
Ischaemic stroke‡
rs62262077 ALCAM 1·17 (1·10–1·24) 6·04 × 10−7 0·99 (0·96–1·02) 0·52 1·03 (0·95–1·12) 0·46 1·03 (0·84–1·26) 0·78 1·02 (0·88–1·18) 0·82 1·01 (0·98–1·03) 0·63 1·03 (1·01–1·06) 0·015
rs10037362 CDH6 1·27 (1·15–1·40) 4·41 × 10−6 0·98 (0·93–1·03) 0·40 0·99 (0·87–1·12) 0·84 0·93 (0·69–1·26) 0·65 0·86 (0·66–1·13) 0·27 0·97 (0·93–1·02) 0·22 1·01 (0·97–1·05) 0·55
rs4448595 NEBL-AS1 0·83 (0·77–0·90) 2·50 × 10−6 1·01 (0·97–1·05) 0·72 1·02 (0·93–1·12) 0·69 0·89 (0·72–1·10) 0·28 0·96 (0·81–1·14) 0·65 1·00 (0·97–1·03) 0·97 0·98 (0·95–1·00) 0·09
rs11833579 NINJ2 1·19 (1·12–1·27) 5·74 × 10−8 0·98 (0·95–1·01) 0·21 0·96 (0·88–1·04) 0·28 1·04 (0·85–1·29) 0·69 0·96 (0·82–1·12) 0·57 0·98 (0·95–1·01) 0·14 1·01 (0·98–1·03) 0·47
rs77858481 SPRY2 1·38 (1·22–1·55) 2·32 × 10−7 0·99 (0·93–1·06) 0·75 0·90 (0·77–1·05) 0·17 1·02 (0·72–1·44) 0·93 0·91 (0·69–1·20) 0·48 0·98 (0·93–1·03) 0·50 1·03 (0·99–1·08) 0·17
Cardioembolic ischaemic stroke§
rs4284256 FCRL3 1·41 (1·22–1·64) 3·13 × 10−6 0·96 (0·90–1·04) 0·31 0·93 (0·78–1·12) 0·45 1·03 (0·69–1·55) 0·88 0·98 (0·75–1·28) 0·90 0·96 (0·90–1·01) 0·13 1·02 (0·97–1·09) 0·41
rs12646447† PITX2 1·53 (1·31–1·80) 1·92 × 10−7 1·39 (1·29–1·50) 3·15 × 10−18 1·17 (0·98–1·41) 0·083 1·62 (1·09–2·42) 0·018 1·04 (0·78–1·37) 0·80 1·36 (1·28–1·44) 1·89 × 10−23 1·37 (1·29–1·46) 4·72 × 10−24
rs72184 ZNF608 1·30 (1·17–1·46) 2·29 × 10−6 1·02 (0·96–1·08) 0·53 0·99 (0·87–1·13) 0·90 0·92 (0·67–1·28) 0·63 1·03 (0·85–1·26) 0·74 1·02 (0·97–1·06) 0·49 1·06 (1·01–1·10) 0·017
rs72794386 SLC12A2 1·67 (1·39–2·00) 4·37 × 10−8 0·97 (0·89–1·06) 0·51 1·09 (0·87–1·37) 0·46 0·95 (0·56–1·62) 0·85 0·78 (0·54–1·14) 0·18 0·96 (0·90–1·03) 0·27 1·06 (0·99–1·14) 0·12
rs1428155 GLRA1 1·28 (1·16–1·43) 3·10 × 10−6 0·97 (0·92–1·03) 0·33 0·95 (0·83–1·08) 0·44 0·90 (0·66–1·24) 0·51 0·99 (0·81–1·21) 0·94 0·99 (0·95–1·03) 0·64 1·02 (0·98–1·07) 0·38
rs7771564 HDGFL1 1·53 (1·28–1·82) 2·10 × 10−6 1·01 (0·92–1·10) 0·87 0·88 (0·70–1·10) 0·25 1·23 (0·77–1·96) 0·39 1·20 (0·89–1·62) 0·24 1·00 (0·93–1·07) 0·97 1·08 (1·01–1·17) 0·031
rs1495081 TUSC3 1·48 (1·25–1·74) 3·09 × 10−6 1·05 (0·98–1·14) 0·18 0·89 (0·72–1·09) 0·25 1·35 (0·84–2·16) 0·21 1·05 (0·79–1·40) 0·73 1·04 (0·98–1·10) 0·24 1·10 (1·03–1·17) 5·07 × 10−3
rs2393938 ZNF239 1·45 (1·24–1·70) 3·47 × 10−6 1·02 (0·94–1·10) 0·68 1·01 (0·84–1·22) 0·88 0·95 (0·60–1·52) 0·84 0·96 (0·71–1·29) 0·76 1·00 (0·94–1·07) 0·95 1·07 (1·01–1·15) 0·029
rs11021485 MAML2 1·60 (1·32–1·94) 1·24 × 10−6 0·94 (0·86–1·03) 0·17 0·77 (0·63–0·95) 0·015 0·51 (0·25–1·04) 0·063 1·06 (0·78–1·43) 0·73 0·92 (0·86–0·99) 0·017 0·99 (0·92–1·07) 0·82
rs710009 DACT1 1·41 (1·22–1·64) 3·62 × 10−6 1·00 (0·92–1·07) 0·93 0·96 (0·80–1·15) 0·68 1·21 (0·80–1·83) 0·37 1·10 (0·84–1·43) 0·50 1·00 (0·94–1·06) 0·96 1·06 (1·00–1·13) 0·048
Non-cardioembolic ischaemic stroke
rs77744591 SPRY2 1·34 (1·18–1·51) 3·44 × 10−6 1·08 (0·96–1·21) 0·19 1·08 (0·84–1·40) 0·53 1·39 (0·74–2·59) 0·30 0·91 (0·47–1·77) 0·78 1·08 (0·99–1·18) 0·80 1·18 (1·09–1·28) 3·22 × 10−5
rs77744591 SPRY2 1·34 (1·18–1·51) 3·44 × 10−6 1·12 (1·02–1·24) 0·023 1·06 (0·80–1·40) 0·68 0·83 (0·52–1·31) 0·42 0·73 (0·24–2·22) 0·56 1·11 (1·02–1·20) 0·16 1·18 (1·10–1·27) 1·08 × 10−5
*

Validationresults from association analyses of ischaemic stroke for SiGN, METASTROKE, and CADISP, and of all stroke for HVH1.

†

Loci that reach genome-wide significance (p<5 × 10−8) in the combined meta-analysis.

‡

Follow-up results from association analyses of ischaemic stroke for SiGN, METASTROKE, HVH1, and CADISP.

§

Validation results from association analyses of cardioembolic ischaemic stroke for SiGN, METASTROKE, HVH1, and CADISP (TOAST subtyping).

Validation results from association analyses of large-vessel ischaemic stroke (first line) and small-vessel ischaemic stroke (second line) for SiGN, METASTROKE, HVH1, and CADISP (TOAST subtyping).