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Multi-ancestry meta-analysis identifies 5 novel loci for ischemic stroke and reveals heterogeneity of effects between sexes and ancestries.
Surakka, Ida; Wu, Kuan-Han; Hornsby, Whitney; Wolford, Brooke N; Shen, Fred; Zhou, Wei; Huffman, Jennifer E; Pandit, Anita; Hu, Yao; Brumpton, Ben; Skogholt, Anne Heidi; Gabrielsen, Maiken E; Walters, Robin G; Hveem, Kristian; Kooperberg, Charles; Zöllner, Sebastian; Wilson, Peter W F; Sutton, Nadia R; Daly, Mark J; Neale, Benjamin M; Willer, Cristen J.
Afiliação
  • Surakka I; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Wu KH; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Hornsby W; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Wolford BN; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Shen F; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Zhou W; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Huffman JE; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Pandit A; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hu Y; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA.
  • Brumpton B; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Skogholt AH; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Gabrielsen ME; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Walters RG; Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
  • Hveem K; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Kooperberg C; Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Zöllner S; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Daly MJ; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Neale BM; HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway.
  • Willer CJ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Cell Genom ; 3(8): 100345, 2023 Aug 09.
Article em En | MEDLINE | ID: mdl-37601974
ABSTRACT
Stroke is the second leading cause of death and disability worldwide. Stroke prevalence varies by sex and ancestry, possibly due to genetic heterogeneity between subgroups. We performed a genome-wide meta-analysis of 16 biobanks across multiple ancestries to study the genetics of ischemic stroke (60,176 cases, 1,310,725 controls) as part of the Global Biobank Meta-analysis Initiative (GBMI) and further combined the results with previously published MegaStroke. Five novel loci for ischemic stroke (LAMC1, CALCRL, PLSCR1, CDKN1A, and SWAP70) were identified after replication in four additional datasets. One previously reported locus showed significant ancestry heterogeneity (ABO), and one showed significant sex heterogeneity (ALDH2). The ALDH2 association was male specific (males p = 1.67e-24, females p = 0.126) and was additionally observed only in the East Asian ancestry (male) samples. These findings emphasize the need for more diverse datasets with large sample sizes to further understand the genetic predisposition of stroke in different ancestry and sex groups.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article