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

Malik, Rainer; Chauhan, Ganesh; Traylor, Matthew; Sargurupremraj, Muralidharan ; Okada, Yukinori; Mishra, Aniket ; Almgren, Peter LU ; Melander, Olle LU ; Engström, Gunnar LU and Lindgren, Arne LU , et al. (2018) In Nature Genetics
Abstract
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... (More)
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. © 2018 The Author(s) (Less)
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Nature Genetics
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14 pages
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Nature Publishing Group
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1546-1718
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fe618d03-4227-425b-a4f0-8b5a776b40c0
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2018-03-20 07:33:39
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@article{fe618d03-4227-425b-a4f0-8b5a776b40c0,
  abstract     = {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. © 2018 The Author(s)},
  author       = {Malik, Rainer and Chauhan, Ganesh and Traylor, Matthew and Sargurupremraj, Muralidharan  and Okada, Yukinori and Mishra, Aniket  and Almgren, Peter and Melander, Olle and Engström, Gunnar and Lindgren, Arne and Delavaran, Hossein and Ilinca, Andreea and Norrving, Bo and , },
  issn         = {1546-1718},
  language     = {eng},
  month        = {03},
  pages        = {14},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes},
  url          = {http://dx.doi.org/},
  year         = {2018},
}