1. Whole-Genome Sequencing Association Analyses of Stroke and Its Subtypes in Ancestrally Diverse Populations From Trans-Omics for Precision Medicine Project
- Author
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Hu, Yao, Haessler, Jeffrey W, Manansala, Regina, Wiggins, Kerri L, Moscati, Arden, Beiser, Alexa, Heard-Costa, Nancy L, Sarnowski, Chloe, Raffield, Laura M, Chung, Jaeyoon, Marini, Sandro, Anderson, Christopher D, Rosand, Jonathan, Xu, Huichun, Sun, Xiao, Kelly, Tanika N, Wong, Quenna, Lange, Leslie A, Rotter, Jerome I, Correa, Adolfo, Vasan, Ramachandran S, Seshadri, Sudha, Rich, Stephen S, Do, Ron, Loos, Ruth JF, Longstreth, William T, Bis, Joshua C, Psaty, Bruce M, Tirschwell, David L, Assimes, Themistocles L, Silver, Brian, Liu, Simin, Jackson, Rebecca, Wassertheil-Smoller, Sylvia, Mitchell, Braxton D, Fornage, Myriam, Auer, Paul L, Reiner, Alex P, Kooperberg, Charles, and Group, the NHLBI Trans-Omics for Precision Medicine Consortium the Trans-Omics for Precision Medicine Stroke Working
- Subjects
Epidemiology ,Health Sciences ,Human Genome ,Neurosciences ,Brain Disorders ,Stroke ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Aged ,Aged ,80 and over ,Female ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Precision Medicine ,Racial Groups ,Whole Genome Sequencing ,atherosclerosis ,blood pressure ,cause of death ,embolic stroke ,sample size ,Trans-Omics for Precision Medicine (TOPMed) Stroke Working Group ,the NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Neurology & Neurosurgery ,Clinical sciences ,Allied health and rehabilitation science - Abstract
Background and purposeStroke is the leading cause of death and long-term disability worldwide. Previous genome-wide association studies identified 51 loci associated with stroke (mostly ischemic) and its subtypes among predominantly European populations. Using whole-genome sequencing in ancestrally diverse populations from the Trans-Omics for Precision Medicine (TOPMed) Program, we aimed to identify novel variants, especially low-frequency or ancestry-specific variants, associated with all stroke, ischemic stroke and its subtypes (large artery, cardioembolic, and small vessel), and hemorrhagic stroke and its subtypes (intracerebral and subarachnoid).MethodsWhole-genome sequencing data were available for 6833 stroke cases and 27 116 controls, including 22 315 European, 7877 Black, 2616 Hispanic/Latino, 850 Asian, 54 Native American, and 237 other ancestry participants. In TOPMed, we performed single variant association analysis examining 40 million common variants and aggregated association analysis focusing on rare variants. We also combined TOPMed European populations with over 28 000 additional European participants from the UK BioBank genome-wide array data through meta-analysis.ResultsIn the single variant association analysis in TOPMed, we identified one novel locus 13q33 for large artery at whole-genome-wide significance (P
- Published
- 2022