- Tytuł:
- Contribution of common genetic variants to risk of early-onset ischemic stroke
- Autorzy:
-
Jimenez-Conde, Jordi
Ryan, Kathleen A.
Luke, Sothear
Gieger, Christian
Pera, Joanna
Thijs, Vincent
Smith, Jennifer A.
Mitchell, Braxton D.
Chong, Michael
Rexrode, Kathryn
Cruchaga, Carlos
Torres-Aguila, Nuria P.
Markus, Hugh S.
Heitsch, Laura
Walters, Robin G.
Li, Jiang
Rosand, Jonathan
Jaworek, Thomas
Kamatani, Yoichiro
Meschia, James F.
Holliday, Elizabeth
Mcardle, Patrick F.
Anderson, Christopher D.
Ilinca, Andreea
Bell, Steven
Cushman, Mary
Gaynor, Brady J.
Muller-Nurasyid, Martina
Putaala, Jukka
Cole, John W.
Engstrom, Gunnar
Grittner, Ulrike
Strbian, Daniel
Kardia, Sharon L.R.
Levi, Christopher R.
Hong, Charles C.
O'Donnell, Martin
Pare, Guillaume
Zand, Ramin
Tuladhar, Anil M.
Faul, Jessica D.
Havulinna, Aki S.
Sacco, Ralph L.
Mcdonough, Caitrin W.
Jern, Christina
Boncoraglio, Giorgio B.
Hu, Jie
Rothwell, Peter M.
Metso, Tiina
Lin, Kuang
Giese, Anne-Katrin
Fecteau, Natalie S.
Jackson, Rebecca D.
Johnson, Julie A.
Ribases, Marta
Attia, John
Veldink, Jan H.
de Leeuw, Frank-Erik
Lemmens, Robin
O'Connor, Timothy D.
Danesh, John
Irvin, Marguerite R.
Perry, James A.
Hochberg, Marc C.
Stine, O. Colin
Fernandez-Cadenas, Israel
Tomppo, Liisa
Abedi, Vida
Grewal, Raji P.
Li, Liming
Sanchez-Mora, Cristina
Lange, Leslie
Ross, Owen A.
Chen, Zhengming
Debette, Stephanie
Wassertheil-Smoller, Sylvia
Stanne, Tara M.
Jacob, Mina A.
Smith, Nicholas L.
Dichgans, Martin
Sudlow, Cathie L.M.
Kittner, Steven J.
Rannikmae, Kristiina
Peddareddygari, Leema R.
Lopez, Haley
Peters, Annette
Benavente, Oscar R.
Weir, David R.
Salomaa, Veikko
Enzinger, Chris
Lindgren, Arne G.
Tatlisumak, Turgut
Durda, Jon Peter
Ray, Debashree
Xu, Huichun
Lee, Jin-Moo
Worrall, Bradford B.
Butterworth, Adam
Słowik, Agnieszka
Soderholm, Martin
Woo, Daniel
Carcel-Marquez, Jara
Duggan, David J.
Maguire, Jane
Koido, Masaru
Sharma, Pankaj
Terao, Chikashi
Malik, Rainer
Schmidt, Reinhold
Amouyel, Philippe
Kubo, Michiaki
Rabionet, Raquel
Tregouet, David-Alexandre
Armstrong, Nicole D.
Rundek, Tatjana - Opis:
- 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 identify the 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 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke 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 (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results: We observed genome-wide significant associations of EOS with 2 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 with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [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 PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with 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.
- Dostawca treści:
- Repozytorium Uniwersytetu Jagiellońskiego
Artykuł