The discovery sample consisted of 15 cohorts of patients with ischaemic stroke who were of European ancestry from Europe, North America, and Australia, together with controls of matched ancestry. All studies used a case-control methodology. Most participating studies were cross-sectional, whereas four were in large, prospective, population-based cohorts (table 1).

Description of cohorts used in analysis by study population

Number of casesNumber of CS casesNumber of LVD casesNumber of SVD casesNumber of controlsAncestryStudy designGenotyping
Discovery cohorts
ARIC3859331638803EuropeanPopulation-basedAffymetrix 6.0
ASGC11622404213101244EuropeanCross-sectionalIllumina 610
BRAINS3612912097444EuropeanCross-sectionalIllumina 660
CHS454147..732817EuropeanPopulation-basedIllumina 370
deCODE239139925524026 970EuropeanCross-sectionalIllumina 317/370
FHS17148....4164EuropeanPopulation-basedAffymetrix 550
GEOS448903754498EuropeanCross-sectionalIllumina HumanOmni1
HPS578......468EuropeanCross-sectionalIllumina 610
HVH56688611731290EuropeanCross-sectionalIllumina 370
ISGS/SWISS10702472292012329EuropeanCross-sectionalIllumina 550/610/660
MGH-GASROS51616995381202EuropeanCross-sectionalAffymetrix 6.0
Milano372257465407EuropeanCross-sectionalIllumina 610/660
Rotterdam367......5396EuropeanPopulation-basedIllumina 550
WTCCC2-Munich1174330346106797EuropeanCross-sectionalIllumina 660
WTCCC2-UK23744604984745175EuropeanCross-sectionalIllumina 660
Total (discovery)12 38923652167189462 004......
Replication cohorts
Barcelona439179110150404EuropeanCross-sectionalSequenom
BSS225119390312EuropeanCross-sectionalSequenom
Copenhagen730......1545EuropeanCross-sectionalTaqMan
ESS276402069940EuropeanCross-sectionalTaqMan/Illumina 610
Glasgow67512591150940EuropeanCross-sectionalSequenom/Illumina 610
Go-Darts*737130259..8424EuropeanCross-sectionalAffymetrix 6.0/Illumina Cardio-metabochip
Graz657116108207848EuropeanCross-sectionalSequenom/Illumina 610
Interstroke*872143198238926EuropeanCross-sectionalIllumina Cardio-metabochip
Krakow1235377152171584EuropeanCross-sectionalSequenom
Leuven4581958363391EuropeanCross-sectionalSequenom
Lund4241402194466EuropeanCross-sectionalSequenom
Munster12324785282241053EuropeanCross-sectionalSequenom
Portugal539......507EuropeanCross-sectionalSequenom
RACE (Pakistan)*13222251951891143PakistaniCross-sectionalIllumina 660
SMART623303681956712EuropeanPopulation-basedSequenom
Sweden87615717775742EuropeanCross-sectionalSequenom
VISP*1725......1047EuropeanCross-sectionalIllumina HumanOmni1
WHI*3024231782099EuropeanPopulation-basedIllumina Omni-Quad
Total (replication)13 34723882434199329 083......

CS=cardioembolic stroke. LVD=large-vessel disease. SVD=small-vessel disease. ARIC=The Atherosclerosis Risk in Communities study. ASGC=Australian Stroke Genetics Collabarative. BRAINS=Bio-Repository of DNA in stroke. CHS=Cardiovascular Health Study. FHS=Framingham Heart Study. GEOS=Genetics of Early-Onset Stroke. HPS=Heart Protection Study. HVH=The Heart and Vascular Health Study. ISGS/SWISS=The Ischemic Stroke Genetics Study/Sibling with Ischaemic Stroke Study. MGH-GASROS=The MGH Genes Affecting Stroke Risk and Outcome Study. WTCCC2-Munich=The Wellcome Trust Case-Control Consortium II Munich. WTCCC2-UK=The Wellcome Trust Case-Control Consortium II UK. BSS=Belgium Stroke Study. ESS=Edinburgh Stroke Study. Go-Darts=Genetics of Diabetes Audit and Research in Tayside Study. RACE=Risk Assessment of Cerebrovascular Events Study, Pakistan. SMART=Second Manifestations of ARTerial disease. VISP=The Vitamin Intervention for Stroke Prevention Trial. WHI=The Women's Health Initiative.

Contributed genome-wide data.

Additionally, 18 cohorts were analysed in the replication phase. These cohorts were included for replication only, most did not have GWAS data available; and those with GWAS data were not available at the time of the discovery analysis. 17 of the included cohorts contained individuals of solely European ancestry, and one contained individuals of Pakistani ancestry (table 1). Most cohorts (16) were cross-sectional, whereas two were population-based.
The appendix includes detailed descriptions of the design and clinical characteristics of the participating studies.
Stroke was defined as a typical clinical syndrome with radiological confirmation. Stroke subtyping was done with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system.18 Where subtyping was done, brain CT or MRI was undertaken for more than 95% of cases in all the discovery cohorts.
Participating studies were approved by relevant institutional review boards, and all participants gave written or oral consent for study participation, including genetic research, as approved by the local institutional body.
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