Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.

2018

Malik, Rainer

Chauhan, Ganesh

Traylor, Matthew

Sargurupremraj, Muralidharan

Okada, Yukinori

Mishra, Aniket

Rutten-Jacobs, Loes

Giese, Anne-Katrin

van der Laan, Sander W

Gretarsdottir, Solveig

Anderson, Christopher D

Anderson, Christopher D

Chong, Michael

Adams, Hieab H H

Ago, Tetsuro

Almgren, Peter

Amouyel, Philippe

Ay, Hakan

Bartz, Traci M

Benavente, Oscar R

Bevan, Steve

Salomaa, Veikko

Bevan, Steve

Boncoraglio, Giorgio B

Brown, Robert D

Butterworth, Adam S

Carrera, Caty

Carty, Cara L

Chasman, Daniel I

Chen, Wei-Min

Cole, John W

Correa, Adolfo

Sapkota, Bishwa R

Boncoraglio, Giorgio B

Cotlarciuc, Ioana

Cruchaga, Carlos

Danesh, John

de Bakker, Paul I W

DeStefano, Anita L

Hoed, Marcel den

Duan, Qing

Engelter, Stefan T

Falcone, Guido J

Schmidt, Reinhold

Gottesman, Rebecca F

Brown, Robert D

Grewal, Raji P

Gudnason, Vilmundur

Gustafsson, Stefan

Haessler, Jeffrey

Harris, Tamara B

Hassan, Ahamad

Havulinna, Aki S

Heckbert, Susan R

Schmidt, Carsten O

Holliday, Elizabeth G

Howard, George

Butterworth, Adam S

Hsu, Fang-Chi

Hyacinth, Hyacinth I

Ikram, M Arfan

Ingelsson, Erik

Irvin, Marguerite R

Jian, Xueqiu

Jiménez-Conde, Jordi

Schminke, Ulf

Johnson, Julie A

Jukema, J Wouter

Kanai, Masahiro

Carrera, Caty

Keene, Keith L

Kissela, Brett M

Kleindorfer, Dawn O

Kooperberg, Charles

Kubo, Michiaki

Lange, Leslie A

Sharma, Pankaj

Langefeld, Carl D

Langenberg, Claudia

Launer, Lenore J

Lee, Jin-Moo

Carty, Cara L

Lemmens, Robin

Leys, Didier

Lewis, Cathryn M

Lin, Wei-Yu

Lindgren, Arne G

Slowik, Agnieszka

Lorentzen, Erik

Magnusson, Patrik K

Maguire, Jane

Manichaikul, Ani

McArdle, Patrick F

Chasman, Daniel I

Meschia, James F

Mitchell, Braxton D

Mosley, Thomas H

Nalls, Michael A

Sudlow, Cathie L M

Ninomiya, Toshiharu

O'Donnell, Martin J

Psaty, Bruce M

Pulit, Sara L

Rannikmäe, Kristiina

Reiner, Alexander P

Chen, Wei-Min

Rexrode, Kathryn M

Rice, Kenneth

Rich, Stephen S

Tanislav, Christian

Ridker, Paul M

Rost, Natalia S

Rothwell, Peter M

Rotter, Jerome I

Rundek, Tatjana

Sacco, Ralph L

Sakaue, Saori

Cole, John W

Sale, Michele M

Salomaa, Veikko

Tatlisumak, Turgut

Sapkota, Bishwa R

Schmidt, Reinhold

Schmidt, Carsten O

Schminke, Ulf

Sharma, Pankaj

Slowik, Agnieszka

Sudlow, Cathie L M

Tanislav, Christian

Correa, Adolfo

Tatlisumak, Turgut

Chong, Michael

Taylor, Kent D

Thijs, Vincent N S

Thorleifsson, Gudmar

Thorsteinsdottir, Unnur

Tiedt, Steffen

Trompet, Stella

Tzourio, Christophe

van Duijn, Cornelia M

Walters, Matthew

Cotlarciuc, Ioana

Taylor, Kent D

Wareham, Nicholas J

Wassertheil-Smoller, Sylvia

Wilson, James G

Wiggins, Kerri L

Yang, Qiong

Yusuf, Salim

Amin, Najaf

Aparicio, Hugo S

Arnett, Donna K

Attia, John

Thijs, Vincent N S

Cruchaga, Carlos

Beiser, Alexa S

Berr, Claudine

Buring, Julie E

Bustamante, Mariana

Caso, Valeria

Cheng, Yu-Ching

Choi, Seung Hoan

Chowhan, Ayesha

Cullell, Natalia

Thorleifsson, Gudmar

Dartigues, Jean-François

Danesh, John

Delavaran, Hossein

Delgado, Pilar

Dörr, Marcus

Engström, Gunnar

Ford, Ian

Gurpreet, Wander S

Hamsten, Anders

Heitsch, Laura

Thorsteinsdottir, Unnur

Hozawa, Atsushi

Ibanez, Laura

de Bakker, Paul I W

Ilinca, Andreea

Ingelsson, Martin

Iwasaki, Motoki

Jackson, Rebecca D

Jood, Katarina

Jousilahti, Pekka

Kaffashian, Sara

Tiedt, Steffen

Kalra, Lalit

Kamouchi, Masahiro

Kitazono, Takanari

DeStefano, Anita L

Kjartansson, Olafur

Kloss, Manja

Koudstaal, Peter J

Krupinski, Jerzy

Labovitz, Daniel L

Laurie, Cathy C

Trompet, Stella

Levi, Christopher R

Li, Linxin

Lind, Lars

Lindgren, Cecilia M

den Hoed, Marcel

Lioutas, Vasileios

Liu, Yong Mei

Lopez, Oscar L

Makoto, Hirata

Martinez-Majander, Nicolas

Tzourio, Christophe

Matsuda, Koichi

Minegishi, Naoko

Montaner, Joan

Morris, Andrew P

Muiño, Elena

Duan, Qing

Müller-Nurasyid, Martina

Norrving, Bo

Ogishima, Soichi

Parati, Eugenio A

van Duijn, Cornelia M

Peddareddygari, Leema Reddy

Pedersen, Nancy L

Pera, Joanna

Perola, Markus

Pezzini, Alessandro

Pileggi, Silvana

Engelter, Stefan T

Rabionet, Raquel

Riba-Llena, Iolanda

Ribasés, Marta

Walters, Matthew

Romero, Jose R

Roquer, Jaume

Rudd, Anthony G

Sarin, Antti-Pekka

Sarju, Ralhan

Sarnowski, Chloe

Sasaki, Makoto

Falcone, Guido J

Satizabal, Claudia L

Satoh, Mamoru

Wareham, Nicholas J

Sattar, Naveed

Sawada, Norie

Sibolt, Gerli

Sigurdsson, Ásgeir

Smith, Albert

Sobue, Kenji

Soriano-Tárraga, Carolina

Stanne, Tara

Gottesman, Rebecca F

Stine, O Colin

Adams, Hieab H H

Stott, David J

Strauch, Konstantin

Takai, Takako

Tanaka, Hideo

Tanno, Kozo

Teumer, Alexander

Tomppo, Liisa

Torres-Aguila, Nuria P

Touze, Emmanuel

Grewal, Raji P

Wassertheil-Smoller, Sylvia

Tsugane, Shoichiro

Uitterlinden, Andre G

Valdimarsson, Einar M

van der Lee, Sven J

Völzke, Henry

Wakai, Kenji

Weir, David

Williams, Stephen R

Wolfe, Charles D A

Wong, Quenna

Wilson, James G

Gudnason, Vilmundur

Xu, Huichun

Yamaji, Taiki

Sanghera, Dharambir K

Melander, Olle

Jern, Christina

Strbian, Daniel

Fernandez-Cadenas, Israel

Longstreth, W T

Rolfs, Arndt

Wiggins, Kerri L

Hata, Jun

Gustafsson, Stefan

Woo, Daniel

Rosand, Jonathan

Pare, Guillaume

Hopewell, Jemma C

Saleheen, Danish

Stefansson, Kari

Worrall, Bradford B

Kittner, Steven J

Yang, Qiong

Seshadri, Sudha

Fornage, Myriam

Haessler, Jeffrey

Markus, Hugh S

Howson, Joanna M M

Kamatani, Yoichiro

Debette, Stephanie

Dichgans, Martin

Harris, Tamara B

Hassan, Ahamad

Yusuf, Salim

Havulinna, Aki S

Heckbert, Susan R

Holliday, Elizabeth G

Howard, George

Hsu, Fang-Chi

Hyacinth, Hyacinth I

Ikram, M Arfan

Ingelsson, Erik

Irvin, Marguerite R

Jian, Xueqiu

Bis, Joshua C

Jiménez-Conde, Jordi

Johnson, Julie A

Jukema, J Wouter

Kanai, Masahiro

Keene, Keith L

Kissela, Brett M

Kleindorfer, Dawn O

Kooperberg, Charles

Kubo, Michiaki

Lange, Leslie A

Pastinen, Tomi

Langefeld, Carl D

Langenberg, Claudia

Launer, Lenore J

Lee, Jin-Moo

Lemmens, Robin

Leys, Didier

Lewis, Cathryn M

Lin, Wei-Yu

Lindgren, Arne G

Lorentzen, Erik

Ruusalepp, Arno

Magnusson, Patrik K

Maguire, Jane

Manichaikul, Ani

McArdle, Patrick F

Meschia, James F

Mitchell, Braxton D

Mosley, Thomas H

Nalls, Michael A

Ninomiya, Toshiharu

O'Donnell, Martin J

Schadt, Eric E

Psaty, Bruce M

Pulit, Sara L

Rannikmäe, Kristiina

Reiner, Alexander P

Rexrode, Kathryn M

Rice, Kenneth

Rich, Stephen S

Ridker, Paul M

Rost, Natalia S

Rothwell, Peter M

Koplev, Simon

Rotter, Jerome I

Rundek, Tatjana

Sacco, Ralph L

Sakaue, Saori

Sale, Michele M

Ago, Tetsuro

Björkegren, Johan L M

Codoni, Veronica

Civelek, Mete

Smith, Nicholas L

Trégouët, David A

Christophersen, Ingrid E

Roselli, Carolina

Lubitz, Steven A

Ellinor, Patrick T

Tai, E Shyong

Almgren, Peter

Kooner, Jaspal S

Kato, Norihiro

He, Jiang

van der Harst, Pim

Elliott, Paul

Chambers, John C

Takeuchi, Fumihiko

Johnson, Andrew D

Sanghera, Dharambir K

Melander, Olle

Amouyel, Philippe

Jern, Christina

Strbian, Daniel

Fernandez-Cadenas, Israel

Longstreth, W T

Rolfs, Arndt

Hata, Jun

Woo, Daniel

Rosand, Jonathan

Pare, Guillaume

Hopewell, Jemma C

Ay, Hakan

Saleheen, Danish

Stefansson, Kari

Worrall, Bradford B

Kittner, Steven J

Seshadri, Sudha

Fornage, Myriam

Markus, Hugh S

Howson, Joanna M M

Kamatani, Yoichiro

Debette, Stephanie

Bartz, Traci M

Dichgans, Martin

Malik, Rainer

Chauhan, Ganesh

Traylor, Matthew

Sargurupremraj, Muralidharan

Okada, Yukinori

Mishra, Aniket

Rutten-Jacobs, Loes

Giese, Anne-Katrin

van der Laan, Sander W

Benavente, Oscar R

Gretarsdottir, Solveig

Journal Article

0000-0001-6624-8621

0000-0002-0311-8472

0000-0003-3223-885X

0000-0001-6888-1404

0000-0003-3687-2508

0000-0002-0473-0241

0000-0001-9088-234X

0000-0002-9501-600X

0000-0002-0276-2899

0000-0001-8081-428X

0000-0001-5894-0351

0000-0002-4787-8959

0000-0003-0372-8585

0000-0002-3246-8359

0000-0001-5165-4408

0000-0002-8249-8476

0000-0002-9267-7988

0000-0002-7315-7899

0000-0002-2502-3669

0000-0003-2749-1279

0000-0002-3658-1375

0000-0002-7892-8808

0000-0002-8586-5614

0000-0002-8141-0284

0000-0001-9084-7800

0000-0002-6141-4712

0000-0001-5267-6756

0000-0002-2067-0533

0000-0002-2713-686X

0000-0002-7511-5684

0000-0003-3185-5661

0000-0002-7531-2354

0000-0001-6193-020X

0000-0001-8748-5597

0000-0002-0654-387X

0000-0003-3687-2508

0000-0003-0372-8585

0000-0002-7315-7899

0000-0002-2502-3669

0000-0002-6614-8417

10.1038/s41588-018-0058-3

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

link

Nature genetics 2018; 50(4): 524-537

Nature genetics