Citations 1
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.