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ABSTRACT: Background and objectives
Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke.Methods
We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS.Results
We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008).Discussion
The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
SUBMITTER: Jaworek T
PROVIDER: S-EPMC9620803 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Jaworek Thomas T Xu Huichun H Gaynor Brady J BJ Cole John W JW Rannikmae Kristiina K Stanne Tara M TM Tomppo Liisa L Abedi Vida V Amouyel Philippe P Armstrong Nicole D ND Attia John J Bell Steven S Benavente Oscar R OR Boncoraglio Giorgio B GB Butterworth Adam A Carcel-Marquez Jara J Chen Zhengming Z Chong Michael M Cruchaga Carlos C Cushman Mary M Danesh John J Debette Stéphanie S Duggan David J DJ Durda Jon Peter JP Engstrom Gunnar G Enzinger Chris C Faul Jessica D JD Fecteau Natalie S NS Fernandez-Cadenas Israel I Gieger Christian C Giese Anne-Katrin AK Grewal Raji P RP Grittner Ulrike U Havulinna Aki S AS Heitsch Laura L Hochberg Marc C MC Holliday Elizabeth E Hu Jie J Hu Jie J Ilinca Andreea A Irvin Marguerite R MR Jackson Rebecca D RD Jacob Mina A MA Rabionet Raquel R Jimenez-Conde Jordi J Johnson Julie A JA Kamatani Yoichiro Y Kardia Sharon L R SLR Koido Masaru M Kubo Michiaki M Lange Leslie L Lee Jin-Moo JM Lemmens Robin R Levi Christopher R CR Li Jiang J Li Liming L Lin Kuang K Lopez Haley H Luke Sothear S Maguire Jane J McArdle Patrick F PF McDonough Caitrin W CW Meschia James F JF Metso Tiina T Müller-Nurasyid Martina M O'Connor Timothy D TD O'Donnell Martin M Peddareddygari Leema R LR Pera Joanna J Perry James A JA Peters Annette A Putaala Jukka J Ray Debashree D Rexrode Kathryn K Ribases Marta M Rosand Jonathan J Rothwell Peter M PM Rundek Tatjana T Ryan Kathleen A KA Sacco Ralph L RL Salomaa Veikko V Sanchez-Mora Cristina C Schmidt Reinhold R Sharma Pankaj P Slowik Agnieszka A Smith Jennifer A JA Smith Nicholas L NL Wassertheil-Smoller Sylvia S Söderholm Martin M Stine O Colin OC Strbian Daniel D Sudlow Cathie L M CLM Tatlisumak Turgut T Terao Chikashi C Thijs Vincent V Torres-Aguila Nuria P NP Trégouët David-Alexandre DA Tuladhar Anil M AM Veldink Jan H JH Walters Robin G RG Weir David R DR Woo Daniel D Worrall Bradford B BB Hong Charles C CC Ross Owen A OA Zand Ramin R Leeuw Frank-Erik de FE Lindgren Arne G AG Pare Guillaume G Anderson Christopher D CD Markus Hugh S HS Jern Christina C Malik Rainer R Dichgans Martin M Mitchell Braxton D BD Kittner Steven J SJ
Neurology 20221017 16
<h4>Background and objectives</h4>Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke.<h4>Methods</h4>We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke control ...[more]