Citations 2
Abstract 154: Sex-specific Genome Wide Association Study Of Early-onset Ischemic Stroke
Leeuw, Frank‐Erik de , Cadenas, Israel Fernández, Słowik, Agnieszka, Conde, Jordi Jiménez, Schmidt, Reinhold, Sharma, Pankaj , Rothwell, Peter M. , Sudlow, Catherine, Debette, Stéphanie , Markus, Hugh S. , Saleheen, Danish , Danesh, John , Zand, Ramin , Worrall, Bradford B. , Woo, Daniel , Lee, Jin-moo, Irvin, Marguerite R. , Rosand, Jonathan, Kamatani, Yoichiro, Xu, Huichun , Kittner, Steven J. , Debette, Stephanie , Zand, Ramin , Tomppo, Liisa , Rannikmäe, Kristiina , Stanne, Tara M. , Putaala, Jukka , Strbian, Daniel , Jern, Christina , Boncoraglio, Giorgio B. , Lindgren, Arne G. , Lemmens, Robin , Melander, Olle , Levi, Christopher , Sudlow, Catherine, Metso, Tiina M. , Paré, Guillaume , Meschia, James F. , Rundek, Tatjana , Lee, Jin‐Moo , McDonough, Caitrin W. , Rexrode, Kathryn M. , Wassertheil-Smoller, Sylvia W , Rosand, Jonathan M. , Gieger, Christian , Müller‐Nurasyid, Martina , Salomaa, Veikko , Kamatani, Yoichiro, Walters, Robin G. , Chen, Zhengming , Dichgans, Martin , Malik, Rainer , Gaynor, Brady J. , Cole, John W. , Mitchell, Braxton D.
Stroke | February 3, 2022 | Volume: 53 | Issue: Suppl_1 | Pages: No page available
Introduction: Genetic studies of early-onset disease have been an effective strategy to identify novel pathways and drug targets generalizable also to later-onset disease. Few studies have investigated the sex-specific genetic associations with early-onset ischemic stroke even though several features of ischemic stroke differ between males and females. We hypothesized that stratifying the GWAS by sex would reveal novel stroke loci. Methods: We performed a transethnic ischemic stroke GWAS of 3,056 female cases and 4,462 male cases < 60 years-old and 16,192 and 16,048 sex-matched controls, respectively, from the Early Onset Stroke Genetics Consortium. Results: We identified a significant association in women with a locus in close proximity to TMX1 , a transmembrane platelet protein that inhibits platelet function. Additionally, we identified 2 other suggestive (P < 5 x 10 -6 ) loci in females (see Table), i.e., at APOH , which encodes beta2-glycoprotein I, an established GWAS locus for lipoprotein(a), and LRFN2 which has been previously reported to associate with obesity-related measures and type II diabetes. We observed suggestive evidence for association in males with MMP3/MMP12 , a known stroke susceptibility locus. Conclusions: Despite a very modest sample size, sex-specific analyses identified suggestive associations at biologically important novel loci in females and a known stroke locus in males. Further studies of sex-specific associations in both early- and later-onset ischemic stroke are needed.
Stroke Genetics Network (SiGN) Study
Arnett, Donna K. , Ay, Hakan , Brown, Robert D. , Benavente, Oscar, Bakker, Paul I. W. de , Dichgans, Martin , Doheny, Kimberly F. , Fornage, Myriam , Grewal, Raji P., Gwinn, Katrina , Conde, Jordi Jiménez, Johnson, Julie A. , Laurie, Cathy C. , Lee, Jin‐Moo , Lindgren, Arne, Markus, Hugh S. , McArdle, Patrick F. , McClure, Leslie A. , Mitchell, Braxton D. , Schmidt, Reinhold , Rexrode, Kathryn M. , Rich, Stephen S. , Rothwell, Peter M. , Sacco, Ralph L., Shuldiner, Alan R. , Słowik, Agnieszka , Sudlow, Cathie , Thijs, Vincent , Woo, Daniel , Worrall, Bradford B. , Wu, Ona , Kittner, Steven J. , collaborators, The SiGN study also includes the following, Anderson, Christopher D. , Andrén, Kerstin , Barrett, Kevin M. , Benner, Thomas, Bentley, Paul , Bevan, Steven, Biffi, Alessandro , Chapman, Sherita , Cheng, Yu‐Ching, Delavaran, Hossein , Gamble, Dale M., Giralt, Eva, Grazer, Anja, Gschwendtner, Andreas, Hegge, Caityln, Heitsch, Laura , Helenius, Johanna, Huq, Mohammed Saiful, Irie, Robert E., Jackson, Rebecca D. , Katschnig, Petra , Katsnelson, Michael , Khoury, Naïm , Kilinc, Selma, Kumar, Gyanendra, Langefeld, Carl D. , Lemmens, Robin , Malik, Shaneela , Melander, Olle , Nordström, Sara , Ois, Ángel , Ossi, Raid G., Peddareddygari, Leema Reddy , Pedersén, Annie , Pucek, Mateusz, Redfors, Petra , Rhodes, J. , Saraf, Neha, Schuerks, Markus, Seiler, Stephan , Sheikh, Huma U., Sparks, Mary J., Stoegerer, Eva, Temple, Ella, Valenti, Raffaella , Weir, David R. , Weissman, Darren, Woodfield, Rebecca, Yiin, Gabriel , Soliman, Elsayed Z. , Cushman, Mary , Kumar, Gyanendra , Bevan, Steve , Meschia, James F. , Cole, John W. , Jern, Christina , Jood, Katarina , Lindgren, Arne, Rosand, Jonathan M. , Rundek, Tatjana , Sharma, Pankaj Kumar , Wassertheil-Smoller, Sylvia W , collaborators, The SiGN study also includes the following, Andsberg, Gunnar , Arsava, Ethem Murat , Bevan, Steven, Brenner, David A. , Deline, Chris A. , Dziedzic, Tomasz , Holmegaard, Lukas , Kilinc, Selma, Kumar, Gyanendra, Labovitz, Daniel , Lanfranconi, Silvia , Li, Linxin , Norrving, Bo , Pera, Joanna , Rannikmäe, Kristiina , Ribasés, Marta , Southerland, Andrew M. , Sunyer, Jordi , Dichgans, Martin , Rich, Stephen S , Lemmens, Robin , Mitchell, Braxton D , Shuldiner, Alan R , Arnett, Donna K , Wu, Ona , Lee, Jin-Moo
Stroke | September 11, 2013 | Volume: 44 | Issue: 10 | Pages: 2694-2702
Background and Purpose— Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods— The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10 296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14 549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research–generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived. Conclusions— The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.