Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
Malik, R
Chauhan, G
Traylor, M
Sargurupremraj, M
Okada, Y
Mishra, A
Rutten-Jacobs, L
Giese, AK
Van Der Laan, SW
Gretarsdottir, S
Anderson, CD
Chong, M
Adams, HHH
Ago, T
Almgren, P
Amouyel, P
Ay, H
Bartz, TM
Benavente, OR
Bevan, S
Boncoraglio, GB
Brown, RD
Butterworth, AS
Carrera, C
Carty, CL
Chasman, DI
Chen, WM
Cole, JW
Correa, A
Cotlarciuc, I
Cruchaga, C
Danesh, J
De Bakker, PIW
Destefano, AL
Den Hoed, M
Duan, Q
Engelter, ST
Falcone, GJ
Gottesman, RF
Grewal, RP
Gudnason, V
Gustafsson, S
Haessler, J
Harris, TB
Hassan, A
Havulinna, AS
Heckbert, SR
Holliday, EG
Howard, G
Hsu, FC
Hyacinth, HI
Ikram, MA
Ingelsson, E
Irvin, MR
Jian, X
Jiménez-Conde, J
Johnson, JA
Jukema, JW
Kanai, M
Keene, KL
Kissela, BM
Kleindorfer, DO
Kooperberg, C
Kubo, M
Lange, LA
Langefeld, CD
Langenberg, C
Launer, LJ
Lee, JM
Lemmens, R
Leys, D
Lewis, CM
Lin, WY
Lindgren, AG
Lorentzen, E
Magnusson, PK
Maguire, J
Manichaikul, A
McArdle, PF
Meschia, JF
Mitchell, BD
Mosley, TH
Nalls, MA
Ninomiya, T
O'Donnell, MJ
Psaty, BM
Pulit, SL
Rannikmäe, K
Reiner, AP
Rexrode, KM
Rice, K
Rich, SS
Ridker, PM
Rost, NS
Rothwell, PM
Rotter, JI
Rundek, T
Sacco, RL
Sakaue, S
Sale, MM
- Publication Type:
- Journal Article
- Citation:
- Nature Genetics, 2018, 50 (4), pp. 524 - 537
- Issue Date:
- 2018-04-01
Closed Access
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s41588-018-0058-3.pdf | Published Version | 1.99 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Malik, R | en_US |
dc.contributor.author | Chauhan, G | en_US |
dc.contributor.author | Traylor, M | en_US |
dc.contributor.author | Sargurupremraj, M | en_US |
dc.contributor.author | Okada, Y | en_US |
dc.contributor.author | Mishra, A | en_US |
dc.contributor.author | Rutten-Jacobs, L | en_US |
dc.contributor.author | Giese, AK | en_US |
dc.contributor.author | Van Der Laan, SW | en_US |
dc.contributor.author | Gretarsdottir, S | en_US |
dc.contributor.author | Anderson, CD | en_US |
dc.contributor.author | Chong, M | en_US |
dc.contributor.author | Adams, HHH | en_US |
dc.contributor.author | Ago, T | en_US |
dc.contributor.author | Almgren, P | en_US |
dc.contributor.author | Amouyel, P | en_US |
dc.contributor.author | Ay, H | en_US |
dc.contributor.author | Bartz, TM | en_US |
dc.contributor.author | Benavente, OR | en_US |
dc.contributor.author | Bevan, S | en_US |
dc.contributor.author | Boncoraglio, GB | en_US |
dc.contributor.author | Brown, RD | en_US |
dc.contributor.author | Butterworth, AS | en_US |
dc.contributor.author | Carrera, C | en_US |
dc.contributor.author | Carty, CL | en_US |
dc.contributor.author | Chasman, DI | en_US |
dc.contributor.author | Chen, WM | en_US |
dc.contributor.author | Cole, JW | en_US |
dc.contributor.author | Correa, A | en_US |
dc.contributor.author | Cotlarciuc, I | en_US |
dc.contributor.author | Cruchaga, C | en_US |
dc.contributor.author | Danesh, J | en_US |
dc.contributor.author | De Bakker, PIW | en_US |
dc.contributor.author | Destefano, AL | en_US |
dc.contributor.author | Den Hoed, M | en_US |
dc.contributor.author | Duan, Q | en_US |
dc.contributor.author | Engelter, ST | en_US |
dc.contributor.author | Falcone, GJ | en_US |
dc.contributor.author | Gottesman, RF | en_US |
dc.contributor.author | Grewal, RP | en_US |
dc.contributor.author | Gudnason, V | en_US |
dc.contributor.author | Gustafsson, S | en_US |
dc.contributor.author | Haessler, J | en_US |
dc.contributor.author | Harris, TB | en_US |
dc.contributor.author | Hassan, A | en_US |
dc.contributor.author | Havulinna, AS | en_US |
dc.contributor.author | Heckbert, SR | en_US |
dc.contributor.author | Holliday, EG | en_US |
dc.contributor.author | Howard, G | en_US |
dc.contributor.author | Hsu, FC | en_US |
dc.contributor.author | Hyacinth, HI | en_US |
dc.contributor.author | Ikram, MA | en_US |
dc.contributor.author | Ingelsson, E | en_US |
dc.contributor.author | Irvin, MR | en_US |
dc.contributor.author | Jian, X | en_US |
dc.contributor.author | Jiménez-Conde, J | en_US |
dc.contributor.author | Johnson, JA | en_US |
dc.contributor.author | Jukema, JW | en_US |
dc.contributor.author | Kanai, M | en_US |
dc.contributor.author | Keene, KL | en_US |
dc.contributor.author | Kissela, BM | en_US |
dc.contributor.author | Kleindorfer, DO | en_US |
dc.contributor.author | Kooperberg, C | en_US |
dc.contributor.author | Kubo, M | en_US |
dc.contributor.author | Lange, LA | en_US |
dc.contributor.author | Langefeld, CD | en_US |
dc.contributor.author | Langenberg, C | en_US |
dc.contributor.author | Launer, LJ | en_US |
dc.contributor.author | Lee, JM | en_US |
dc.contributor.author | Lemmens, R | en_US |
dc.contributor.author | Leys, D | en_US |
dc.contributor.author | Lewis, CM | en_US |
dc.contributor.author | Lin, WY | en_US |
dc.contributor.author | Lindgren, AG | en_US |
dc.contributor.author | Lorentzen, E | en_US |
dc.contributor.author | Magnusson, PK | en_US |
dc.contributor.author |
Maguire, J |
en_US |
dc.contributor.author | Manichaikul, A | en_US |
dc.contributor.author | McArdle, PF | en_US |
dc.contributor.author | Meschia, JF | en_US |
dc.contributor.author | Mitchell, BD | en_US |
dc.contributor.author | Mosley, TH | en_US |
dc.contributor.author | Nalls, MA | en_US |
dc.contributor.author | Ninomiya, T | en_US |
dc.contributor.author | O'Donnell, MJ | en_US |
dc.contributor.author | Psaty, BM | en_US |
dc.contributor.author | Pulit, SL | en_US |
dc.contributor.author | Rannikmäe, K | en_US |
dc.contributor.author | Reiner, AP | en_US |
dc.contributor.author | Rexrode, KM | en_US |
dc.contributor.author | Rice, K | en_US |
dc.contributor.author | Rich, SS | en_US |
dc.contributor.author | Ridker, PM | en_US |
dc.contributor.author | Rost, NS | en_US |
dc.contributor.author | Rothwell, PM | en_US |
dc.contributor.author | Rotter, JI | en_US |
dc.contributor.author | Rundek, T | en_US |
dc.contributor.author | Sacco, RL | en_US |
dc.contributor.author | Sakaue, S | en_US |
dc.contributor.author | Sale, MM | en_US |
dc.date.available | 2018-01-08 | en_US |
dc.date.issued | 2018-04-01 | en_US |
dc.identifier.citation | Nature Genetics, 2018, 50 (4), pp. 524 - 537 | en_US |
dc.identifier.issn | 1061-4036 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/129307 | |
dc.description.abstract | © 2018 The Author(s). 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. | en_US |
dc.relation.ispartof | Nature Genetics | en_US |
dc.relation.isbasedon | 10.1038/s41588-018-0058-3 | en_US |
dc.subject.classification | Developmental Biology | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Genetic Predisposition to Disease | en_US |
dc.subject.mesh | Risk Factors | en_US |
dc.subject.mesh | Computational Biology | en_US |
dc.subject.mesh | Epigenesis, Genetic | en_US |
dc.subject.mesh | Linkage Disequilibrium | en_US |
dc.subject.mesh | Polymorphism, Single Nucleotide | en_US |
dc.subject.mesh | Models, Genetic | en_US |
dc.subject.mesh | Databases, Genetic | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Gene Regulatory Networks | en_US |
dc.subject.mesh | Stroke | en_US |
dc.subject.mesh | INDEL Mutation | en_US |
dc.subject.mesh | Genome-Wide Association Study | en_US |
dc.subject.mesh | Genetic Loci | en_US |
dc.title | Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 4 | en_US |
utslib.citation.volume | 50 | en_US |
utslib.for | 1117 Public Health and Health Services | en_US |
utslib.for | 1102 Cardiorespiratory Medicine and Haematology | en_US |
utslib.for | 06 Biological Sciences | en_US |
utslib.for | 11 Medical and Health Sciences | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Health | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Health/Nursing | |
utslib.copyright.status | closed_access | |
pubs.issue | 4 | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 50 | en_US |
Abstract:
© 2018 The Author(s). 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.
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