The EPIC-Norfolk Study
Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
Nature genetics 2017 ; 50: 524-537.
Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Van Der Laan SW, Chong M, Almgren P, Amouyel P, Bartz TM, Bevan S, Butterworth AS, Chasman DI, Chen WM, Correa A, Cruchaga C, Danesh J, de Bakker PIW, den Hoed M, Duan Q, Gudnason V, Gustafsson S, Haessler J, Harris TB, Havulinna AS, Heckbert SR, Holliday EG, Hsu FC, Ikram MA, Ingelsson E, Irvin MR, Jukema JW, Keene KL, Kooperberg C, Kubo M, Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lin WY, Magnusson PK, Maguire J, Manichaikul A, McArdle PF, Mitchell BD, Nalls MA, Psaty BM, Reiner AP, Rice K, Rich SS, Ridker PM, Rotter JI, Sale MM, Salomaa V, Schmidt R, Schmidt CO, Schminke U, Taylor KD, Thorleifsson G, Thorsteinsdottir U, Trompet S, Tzourio C, van Duijn CM, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL, Yang Q, Yusuf S, Bis JC, Ruusalepp A, Schadt EE, Björkegren JLM, Smith NL, Trégouët DA, Lubitz SA, Ellinor PT, Tai ES, Kooner JS, Kato N, van der Harst P, Elliott P, Chambers JC, Takeuchi F, Johnson AD, Sanghera DK, Melander O, Pare G, Hopewell JC, Saleheen D, Stefansson K, Worrall BB, Kittner SJ, Seshadri S, Fornage M, Markus HS, Howson JMM, Kamatani Y, Debette S, and Dichgans M
DOI : 10.1038/s41588-018-0058-3
PubMed ID : 29531354
PMCID : PMC5968830
URL : https://pubmed.ncbi.nlm.nih.gov/29531354/
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.