1. Sex-specific Genome Wide Association Study Of Early-onset Ischemic Stroke
- Author
-
Tomppo, Liisa, Rannikmae, Kristiina, Stanne, Tara M., Putaala, Jukka, Strbian, Daniel, Jern, Christina, de Leeuw, Frank Erik, Cadenas, Israel Fernandez, Slowik, Agnieszka M., Boncoraglio, Giorgio, Lindgren, Arne, Conde, Jordi J., Schmidt, Reinhold, Sharma, Pankaj, Lemmens, Robin, Melander, Olle, Rothwell, Peter, Levi, Christopher, Sudlow, Catherine, Debette, Stephanie, Metso, Tiina, Pare, Guillaume, Markus, Hugh, Saleheen, Danish, Danesh, John, Zand, Ramin, Worrall, Bradford B., Meschia, James F., Rundek, Tatjana, Woo, Daniel, Lee, Jin Moo, Irvin, Marguerite R., Mcdonough, Caitrin W., Rexrode, Kathryn M., Wassertheil-Smoller, Sylvia W., Rosand, Jonathan, Gieger, Christian, Muller-Nurasyid, Martina, Salomaa, Veikko V., Kamatani, Yoichiro, Walters, Robin, Chen, Zhengming, Dichgans, Martin, Malik, Rainer, Gaynor, Brady, Cole, John, Xu, Huichun, Mitchell, Braxton D., Kittner, Steven J., Early-Onset Stroke, Consortium, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Ischemic stroke ,Gender differences ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Genome-wide association studies (GWAS) - Abstract
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.
- Published
- 2022