Stroke genetics informs drug discovery and risk prediction across ancestries.
Mishra A., Malik R., Hachiya T., Jürgenson T., Namba S., Posner DC., Kamanu FK., Koido M., Le Grand Q., Shi M., He Y., Georgakis MK., Caro I., Krebs K., Liaw Y-C., Vaura FC., Lin K., Winsvold BS., Srinivasasainagendra V., Parodi L., Bae H-J., Chauhan G., Chong MR., Tomppo L., Akinyemi R., Roshchupkin GV., Habib N., Jee YH., Thomassen JQ., Abedi V., Cárcel-Márquez J., Nygaard M., Leonard HL., Yang C., Yonova-Doing E., Knol MJ., Lewis AJ., Judy RL., Ago T., Amouyel P., Armstrong ND., Bakker MK., Bartz TM., Bennett DA., Bis JC., Bordes C., Børte S., Cain A., Ridker PM., Cho K., Chen Z., Cruchaga C., Cole JW., de Jager PL., de Cid R., Endres M., Ferreira LE., Geerlings MI., Gasca NC., Gudnason V., Hata J., He J., Heath AK., Ho Y-L., Havulinna AS., Hopewell JC., Hyacinth HI., Inouye M., Jacob MA., Jeon CE., Jern C., Kamouchi M., Keene KL., Kitazono T., Kittner SJ., Konuma T., Kumar A., Lacaze P., Launer LJ., Lee K-J., Lepik K., Li J., Li L., Manichaikul A., Markus HS., Marston NA., Meitinger T., Mitchell BD., Montellano FA., Morisaki T., Mosley TH., Nalls MA., Nordestgaard BG., O'Donnell MJ., Okada Y., Onland-Moret NC., Ovbiagele B., Peters A., Psaty BM., Rich SS., Rosand J., Sabatine MS., Sacco RL., Saleheen D., Sandset EC., Salomaa V., Sargurupremraj M., Sasaki M., Satizabal CL., Schmidt CO., Shimizu A., Smith NL., Sloane KL., Sutoh Y., Sun YV., Tanno K., Tiedt S., Tatlisumak T., Torres-Aguila NP., Tiwari HK., Trégouët D-A., Trompet S., Tuladhar AM., Tybjærg-Hansen A., van Vugt M., Vibo R., Verma SS., Wiggins KL., Wennberg P., Woo D., Wilson PWF., Xu H., Yang Q., Yoon K., COMPASS Consortium None., INVENT Consortium None., Dutch Parelsnoer Initiative (PSI) Cerebrovascular Disease Study Group None., Estonian Biobank None., PRECISEQ Consortium None., FinnGen Consortium None., NINDS Stroke Genetics Network (SiGN) None., MEGASTROKE Consortium None., SIREN Consortium None., China Kadoorie Biobank Collaborative Group None., VA Million Veteran Program None., International Stroke Genetics Consortium (ISGC) None., Biobank Japan None., CHARGE Consortium None., GIGASTROKE Consortium None., Millwood IY., Gieger C., Ninomiya T., Grabe HJ., Jukema JW., Rissanen IL., Strbian D., Kim YJ., Chen P-H., Mayerhofer E., Howson JMM., Irvin MR., Adams H., Wassertheil-Smoller S., Christensen K., Ikram MA., Rundek T., Worrall BB., Lathrop GM., Riaz M., Simonsick EM., Kõrv J., França PHC., Zand R., Prasad K., Frikke-Schmidt R., de Leeuw F-E., Liman T., Haeusler KG., Ruigrok YM., Heuschmann PU., Longstreth WT., Jung KJ., Bastarache L., Paré G., Damrauer SM., Chasman DI., Rotter JI., Anderson CD., Zwart J-A., Niiranen TJ., Fornage M., Liaw Y-P., Seshadri S., Fernández-Cadenas I., Walters RG., Ruff CT., Owolabi MO., Huffman JE., Milani L., Kamatani Y., Dichgans M., Debette S.
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P