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

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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; Melander, Olle; Engström, Gunnar; Lindgren, Arne; Delavaran, Hossein; Ilinca, Andreea; Norrving, Bo; MEGASTROKE Consortium.

I: Nature Genetics, Vol. 50, Nr. 4, 04.2018, s. 524-537.

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Malik, Rainer ; Chauhan, Ganesh ; Traylor, Matthew ; Sargurupremraj, Muralidharan ; Okada, Yukinori ; Mishra, Aniket ; Almgren, Peter ; Melander, Olle ; Engström, Gunnar ; Lindgren, Arne ; Delavaran, Hossein ; Ilinca, Andreea ; Norrving, Bo ; MEGASTROKE Consortium. / Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. I: Nature Genetics. 2018 ; Vol. 50, Nr. 4. s. 524-537.

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TY - JOUR

T1 - Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

AU - Malik, Rainer

AU - Chauhan, Ganesh

AU - Traylor, Matthew

AU - Sargurupremraj, Muralidharan

AU - Okada, Yukinori

AU - Mishra, Aniket

AU - Almgren, Peter

AU - Melander, Olle

AU - Engström, Gunnar

AU - Lindgren, Arne

AU - Delavaran, Hossein

AU - Ilinca, Andreea

AU - Norrving, Bo

AU - MEGASTROKE Consortium

N1 - Export Date: 20 March 2018 Article in Press

PY - 2018/4

Y1 - 2018/4

N2 - 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)

AB - 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)

UR - https://doi.org/10.1038/s41588-019-0449-0

U2 - 10.1038/s41588-018-0058-3

DO - 10.1038/s41588-018-0058-3

M3 - Article

C2 - 29531354

VL - 50

SP - 524

EP - 537

JO - Nature Genetics

JF - Nature Genetics

SN - 1546-1718

IS - 4

ER -