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Multi-ancestry genetic analysis of gene regulation in coronary arteries prioritizes disease risk loci.
Hodonsky, Chani J; Turner, Adam W; Khan, Mohammad Daud; Barrientos, Nelson B; Methorst, Ruben; Ma, Lijiang; Lopez, Nicolas G; Mosquera, Jose Verdezoto; Auguste, Gaëlle; Farber, Emily; Ma, Wei Feng; Wong, Doris; Onengut-Gumuscu, Suna; Kavousi, Maryam; Peyser, Patricia A; van der Laan, Sander W; Leeper, Nicholas J; Kovacic, Jason C; Björkegren, Johan L M; Miller, Clint L.
Afiliação
  • Hodonsky CJ; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Turner AW; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Khan MD; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Barrientos NB; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Methorst R; Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.
  • Ma L; Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Lopez NG; Division of Vascular Surgery, Department of Surgery, Stanford University, Stanford, CA 94305, USA.
  • Mosquera JV; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
  • Auguste G; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Farber E; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Ma WF; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Medical Scientist Training Program, Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
  • Wong D; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
  • Onengut-Gumuscu S; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Kavousi M; Department of Epidemiology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
  • Peyser PA; Department of Epidemiology, University of Michigan, Ann Arbor, MI 48019, USA.
  • van der Laan SW; Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.
  • Leeper NJ; Division of Vascular Surgery, Department of Surgery, Stanford University, Stanford, CA 94305, USA.
  • Kovacic JC; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
  • Björkegren JLM; Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Huddinge, Karolinska Institutet, 141 52 Huddinge, Sweden.
  • Miller CL; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Division of Vascular Surgery, Department of Surgery, Stanford University, Stanford, CA 94305, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA. Electronic addre
Cell Genom ; 4(1): 100465, 2024 Jan 10.
Article em En | MEDLINE | ID: mdl-38190101
ABSTRACT
Genome-wide association studies (GWASs) have identified hundreds of risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWASs, and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotypes to identify quantitative trait loci for expression (eQTLs) and splicing (sQTLs) in coronary arteries from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported in coronary artery; 19% exhibited cell-type-specific expression. Colocalization revealed subgroups of eGenes unique to CAD and blood pressure GWAS. Fine-mapping highlighted additional eGenes, including TBX20 and IL5. We also identified sQTLs for 1,690 genes, among which TOR1AIP1 and ULK3 sQTLs demonstrated the importance of evaluating splicing to accurately identify disease-relevant isoform expression. Our work provides a patient-derived coronary artery eQTL resource and exemplifies the need for diverse study populations and multifaceted approaches to characterize gene regulation in disease processes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vasos Coronários / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vasos Coronários / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article