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Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.
Andreassen, Ole A; Desikan, Rahul S; Wang, Yunpeng; Thompson, Wesley K; Schork, Andrew J; Zuber, Verena; Doncheva, Nadezhda T; Ellinghaus, Eva; Albrecht, Mario; Mattingsdal, Morten; Franke, Andre; Lie, Benedicte A; Mills, Ian G; Mills, Ian; Aukrust, Pål; McEvoy, Linda K; Djurovic, Srdjan; Karlsen, Tom H; Dale, Anders M.
Afiliación
  • Andreassen OA; NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, United States of America.
  • Desikan RS; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Department of Radiology, University of California San Diego, La Jolla, CA 92093, United States of America.
  • Wang Y; NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of Ameri
  • Thompson WK; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, United States of America.
  • Schork AJ; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Cognitive Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, United States of America; Center for Human Development, University of California San Diego, La
  • Zuber V; NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospita
  • Doncheva NT; Max Planck Institute for Informatics, 66123 Saarbrücken, Germany.
  • Ellinghaus E; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
  • Albrecht M; Max Planck Institute for Informatics, 66123 Saarbrücken, Germany; Department of Bioinformatics, Institute of Biometrics and Medical Informatics, University Medicine Greifswald, 17475 Greifswald, Germany; Institute for Knowledge Discovery, Graz University of Technology, 8010 Graz, Austria; BioTechMed
  • Mattingsdal M; NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Sørlandet Hospital, 3000 Kristiansand, Norway.
  • Franke A; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
  • Lie BA; BioTechMed-Graz, 8010 Graz, Austria.
  • Mills I; Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, 0407 Oslo, Norway; Department of Cancer Prevention, Institute of Cancer Research and Department of Urology, Oslo University Hospital, 0407 Oslo, Norway.
  • Aukrust P; Department of Medical Genetics, University of Oslo and Oslo University Hospital, 0407 Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, 0407 Oslo Norway.
  • McEvoy LK; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Department of Radiology, University of California San Diego, La Jolla, CA 92093, United States of America.
  • Djurovic S; NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, 0407 Oslo, Norway; Department of Medical Genetics, University of Oslo and Oslo University Hospital, 0407 Oslo, Norway.
  • Karlsen TH; K.G.Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, 0407 Oslo, Norway; Division of Gastroenterology, Institute of Medicine, University of Bergen, 5000 Bergen, Norway; Norw
  • Dale AM; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, United States of America; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, United States of America; Department of Radiology, University of California San Diego, La Jolla, CA 92093
PLoS One ; 10(4): e0123057, 2015.
Article en En | MEDLINE | ID: mdl-25853426
Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Triglicéridos / Lipoproteínas LDL Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Triglicéridos / Lipoproteínas LDL Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos