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A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.
Akbari, Parsa; Vuckovic, Dragana; Stefanucci, Luca; Jiang, Tao; Kundu, Kousik; Kreuzhuber, Roman; Bao, Erik L; Collins, Janine H; Downes, Kate; Grassi, Luigi; Guerrero, Jose A; Kaptoge, Stephen; Knight, Julian C; Meacham, Stuart; Sambrook, Jennifer; Seyres, Denis; Stegle, Oliver; Verboon, Jeffrey M; Walter, Klaudia; Watkins, Nicholas A; Danesh, John; Roberts, David J; Di Angelantonio, Emanuele; Sankaran, Vijay G; Frontini, Mattia; Burgess, Stephen; Kuijpers, Taco; Peters, James E; Butterworth, Adam S; Ouwehand, Willem H; Soranzo, Nicole; Astle, William J.
Affiliation
  • Akbari P; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Wort's Causeway, Cambridge, CB1 8RN, UK.
  • Vuckovic D; Department of Human Genetics, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1HH, UK.
  • Stefanucci L; Medical Research Council Biostatistics Unit, University of Cambridge, East Forvie Building, Cambridge Biomedical Campus, Forvie Site, Robinson Way, Cambridge, CB2 0SR, UK.
  • Jiang T; The National Institute for Health and Care Research Blood and Transplant Unit in Donor Health and Genomics, Strangeways Research Laboratory, Strangeways Research Laboratory, University of Cambridge, Wort's Causeway, Cambridge, CB1 8RN, UK.
  • Kundu K; Department of Human Genetics, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1HH, UK.
  • Kreuzhuber R; The National Institute for Health and Care Research Blood and Transplant Unit in Donor Health and Genomics, Strangeways Research Laboratory, Strangeways Research Laboratory, University of Cambridge, Wort's Causeway, Cambridge, CB1 8RN, UK.
  • Bao EL; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Collins JH; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Downes K; National Health Service Blood and Transplant, Cambridge Centre, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Grassi L; British Heart Foundation Centre of Research Excellence, University of Cambridge, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Guerrero JA; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Wort's Causeway, Cambridge, CB1 8RN, UK.
  • Kaptoge S; The National Institute for Health and Care Research Blood and Transplant Unit in Donor Health and Genomics, Strangeways Research Laboratory, Strangeways Research Laboratory, University of Cambridge, Wort's Causeway, Cambridge, CB1 8RN, UK.
  • Knight JC; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, CB2 0BB, UK.
  • Meacham S; Department of Human Genetics, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1HH, UK.
  • Sambrook J; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Seyres D; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Stegle O; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA, 02115, USA.
  • Verboon JM; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA, 02115, USA.
  • Walter K; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA.
  • Watkins NA; Harvard-MIT Health Sciences and Technology, Harvard Medical School, 77 Massachusetts Ave, Cambridge, MA, 02139, USA.
  • Danesh J; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Roberts DJ; National Health Service Blood and Transplant, Cambridge Centre, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Di Angelantonio E; Department of Haematology, Barts Health National Health Service Trust, London, E1 1BB, UK.
  • Sankaran VG; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Frontini M; National Health Service Blood and Transplant, Cambridge Centre, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Burgess S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Kuijpers T; National Health Service Blood and Transplant, Cambridge Centre, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Peters JE; National Institute for Health and Care Research Cambridge BioResource, Box 229, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Butterworth AS; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Ouwehand WH; National Health Service Blood and Transplant, Cambridge Centre, Cambridge Biomedical Campus, Long Road, Cambridge, CB2 0PT, UK.
  • Soranzo N; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Wort's Causeway, Cambridge, CB1 8RN, UK.
  • Astle WJ; The National Institute for Health and Care Research Blood and Transplant Unit in Donor Health and Genomics, Strangeways Research Laboratory, Strangeways Research Laboratory, University of Cambridge, Wort's Causeway, Cambridge, CB1 8RN, UK.
Nat Commun ; 14(1): 5023, 2023 08 18.
Article de En | MEDLINE | ID: mdl-37596262
Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Protéomique / Étude d'association pangénomique Type d'étude: Prognostic_studies / Risk_factors_studies Langue: En Journal: Nat Commun Sujet du journal: BIOLOGIA / CIENCIA Année: 2023 Type de document: Article Pays de publication: Royaume-Uni
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Protéomique / Étude d'association pangénomique Type d'étude: Prognostic_studies / Risk_factors_studies Langue: En Journal: Nat Commun Sujet du journal: BIOLOGIA / CIENCIA Année: 2023 Type de document: Article Pays de publication: Royaume-Uni