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Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.
Lo Faro, Valeria; Bhattacharya, Arjun; Zhou, Wei; Zhou, Dan; Wang, Ying; Läll, Kristi; Kanai, Masahiro; Lopera-Maya, Esteban; Straub, Peter; Pawar, Priyanka; Tao, Ran; Zhong, Xue; Namba, Shinichi; Sanna, Serena; Nolte, Ilja M; Okada, Yukinori; Ingold, Nathan; MacGregor, Stuart; Snieder, Harold; Surakka, Ida; Shortt, Jonathan; Gignoux, Chris; Rafaels, Nicholas; Crooks, Kristy; Verma, Anurag; Verma, Shefali S; Guare, Lindsay; Rader, Daniel J; Willer, Cristen; Martin, Alicia R; Brantley, Milam A; Gamazon, Eric R; Jansonius, Nomdo M; Joos, Karen; Cox, Nancy J; Hirbo, Jibril.
Afiliação
  • Lo Faro V; Department of Ophthalmology, Amsterdam University Medical Center (AMC), Amsterdam, the Netherlands; Department of Clinical Genetics, Amsterdam University Medical Center (AMC), Amsterdam, the Netherlands; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala Universit
  • Bhattacharya A; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Zhou W; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Zhou D; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Wang Y; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Läll K; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Kanai M; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department o
  • Lopera-Maya E; University of Groningen, UMCG, Department of Genetics, Groningen, the Netherlands.
  • Straub P; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Pawar P; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Tao R; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Zhong X; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Namba S; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
  • Sanna S; University of Groningen, UMCG, Department of Genetics, Groningen, the Netherlands; Institute for Genetics and Biomedical Research (IRGB), National Research Council (CNR), Cagliari, Italy.
  • Nolte IM; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Okada Y; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka, Japan; Integr
  • Ingold N; Statistical Genetics, QIMR Berghofer Medical Research Institute, Queensland University of Technology, Brisbane, QLD, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
  • MacGregor S; Statistical Genetics, QIMR Berghofer Medical Research Institute, Queensland University of Technology, Brisbane, QLD, Australia.
  • Snieder H; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Surakka I; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Shortt J; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Gignoux C; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Rafaels N; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Crooks K; Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Verma A; Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
  • Verma SS; Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA.
  • Guare L; Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA; Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA.
  • Rader DJ; Department of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania, Philadelphia
  • Willer C; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA; Department of Human Genetics, Un
  • Martin AR; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Brantley MA; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Gamazon ER; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Jansonius NM; Department of Ophthalmology, Amsterdam University Medical Center (AMC), Amsterdam, the Netherlands.
  • Joos K; Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Cox NJ; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Hirbo J; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: jibril.hirbo@vumc.org.
Cell Rep Med ; 5(2): 101430, 2024 Feb 20.
Article em En | MEDLINE | ID: mdl-38382466
ABSTRACT
Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441 cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037 cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glaucoma de Ângulo Aberto / Predisposição Genética para Doença Limite: Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glaucoma de Ângulo Aberto / Predisposição Genética para Doença Limite: Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article