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Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.
Wiley, Mandi M; Khatri, Bhuwan; Joachims, Michelle L; Tessneer, Kandice L; Stolarczyk, Anna M; Rasmussen, Astrid; Anaya, Juan-Manuel; Aqrawi, Lara A; Bae, Sang-Cheol; Baecklund, Eva; Björk, Albin; Brun, Johan G; Bucher, Sara Magnusson; Dand, Nick; Eloranta, Maija-Leena; Engelke, Fiona; Forsblad-d'Elia, Helena; Fugmann, Cecilia; Glenn, Stuart B; Gong, Chen; Gottenberg, Jacques-Eric; Hammenfors, Daniel; Imgenberg-Kreuz, Juliana; Jensen, Janicke Liaaen; Johnsen, Svein Joar Auglænd; Jonsson, Malin V; Kelly, Jennifer A; Khanam, Sharmily; Kim, Kwangwoo; Kvarnström, Marika; Mandl, Thomas; Martín, Javier; Morris, David L; Nocturne, Gaetane; Norheim, Katrine Brække; Olsson, Peter; Palm, Øyvind; Pers, Jacques-Olivier; Rhodus, Nelson L; Sjöwall, Christopher; Skarstein, Kathrine; Taylor, Kimberly E; Tombleson, Phil; Thorlacius, Gudny Ella; Venuturupalli, Swamy; Vital, Edward M; Wallace, Daniel J; Grundahl, Kiely M; Radfar, Lida; Brennan, Michael T.
Afiliação
  • Wiley MM; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
  • Khatri B; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
  • Joachims ML; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
  • Tessneer KL; Arthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, Oklahoma, USA.
  • Stolarczyk AM; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
  • Rasmussen A; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
  • Anaya JM; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
  • Aqrawi LA; Universidad del Rosario, Bogotá, Colombia.
  • Bae SC; Department of Health Sciences, Kristiania University College, Oslo, Norway.
  • Baecklund E; University of Oslo, Norway.
  • Björk A; Hanyang University, Seoul, Republic of Korea.
  • Brun JG; Uppsala University, Uppsala, Sweden.
  • Bucher SM; Karolinska Institutet, Solna, Sweden.
  • Dand N; University of Bergen, Bergen, Norway.
  • Eloranta ML; Haukeland University Hospital, Bergen, Norway.
  • Engelke F; Örebro University, Örebro, Sweden.
  • Forsblad-d'Elia H; King's College London, London, United Kingdom.
  • Fugmann C; Uppsala University, Uppsala, Sweden.
  • Glenn SB; Hannover Medical School, Hannover, Germany.
  • Gong C; University of Gothenburg, Gothenburg, Sweden.
  • Gottenberg JE; Uppsala University, Uppsala, Sweden.
  • Hammenfors D; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
  • Imgenberg-Kreuz J; King's College London, London, United Kingdom.
  • Jensen JL; Strasbourg University Hospitals, Strasbourg, France.
  • Johnsen SJA; Haukeland University Hospital, Bergen, Norway.
  • Jonsson MV; Uppsala University, Uppsala, Sweden.
  • Kelly JA; University of Oslo, Norway.
  • Khanam S; Stavanger University Hospital, Stavanger, Norway.
  • Kim K; University of Bergen, Bergen, Norway.
  • Kvarnström M; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, Oklahoma, USA.
  • Mandl T; Arthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, Oklahoma, USA.
  • Martín J; Kyung Hee University, Seoul, Republic of Korea.
  • Morris DL; Karolinska Institutet, Solna, Sweden.
  • Nocturne G; Lund University, Malmö, Sweden.
  • Norheim KB; Instituto de Biomedicina y Parasitología López-Neyra, Granada, Spain.
  • Olsson P; King's College London, London, United Kingdom.
  • Palm Ø; Université Paris-Saclay, Paris, France.
  • Pers JO; Assistance Publique - Hôpitaux de Paris, Hôpital Bicêtre, Paris, France.
  • Rhodus NL; Stavanger University Hospital, Stavanger, Norway.
  • Sjöwall C; Lund University, Malmö, Sweden.
  • Skarstein K; Oslo University Hospital, Oslo, Norway.
  • Taylor KE; LBAI, UMR1227, University of Brest, Inserm, Brest, France.
  • Tombleson P; University of Minnesota Medical School, Minnesota, USA.
  • Thorlacius GE; Linköping University, Linköping, Sweden.
  • Venuturupalli S; University of Bergen, Bergen, Norway.
  • Vital EM; University of California San Francisco, San Francisco, California, USA.
  • Wallace DJ; King's College London, London, United Kingdom.
  • Grundahl KM; Karolinska Institutet, Solna, Sweden.
  • Radfar L; Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Brennan MT; University of Leeds, Leeds, United Kingdom.
bioRxiv ; 2023 Oct 06.
Article em En | MEDLINE | ID: mdl-39071447
ABSTRACT
Fine mapping and bioinformatic analysis of the DDX6-CXCR5 genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on DDX6 and CXCR5 expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including lnc-PHLDB1-1. Collectively, functional characterization implicated the risk alleles of these SNPs as modulators of promoter and/or enhancer activities that regulate cell type-specific expression of DDX6, CXCR5, and lnc-PHLDB1-1, among others. Further, these findings emphasize the importance of exploring the functional significance of SNPs in the context of complex chromatin architecture in disease-relevant cell types and tissues.
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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos