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A Possible Mechanis...
A Possible Mechanism behind Autoimmune Disorders Discovered By Genome-Wide Linkage and Association Analysis in Celiac Disease
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- Östensson, Malin, 1984 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg,Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden
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- Montén, Caroline (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden
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- Bacelis, Jonas, 1984 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,University of Gothenburg,Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
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- Gudjonsdottir, Audur, 1959 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics,University of Gothenburg,Queen Silvia Children’s Hospital, Sahlgrenska Academy at the University of Gothenburg, Department of Pediatrics, Gothenburg, Sweden
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- Adamovic, Svetlana, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,University of Gothenburg,Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
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- Ek, Johan (author)
- Buskerud Central Hospital, Department of Pediatrics, Drammen, Norway
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- Ascher, Henry, 1953 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa,Institute of Medicine, School of Public Health and Community Medicine,University of Gothenburg,Sahlgrenska Academy at the University of Gothenburg, Department of Public Health and Community Medicine, Unit of Social Medicine, Gothenburg, Sweden
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- Pollak, Elisabet (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,University of Gothenburg,Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
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- Arnell, Henrik (author)
- Karolinska Institutet,Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital and Division of Pediatrics, CLINTEC, Karolinska Institutet, Stockholm, Sweden
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- Browaldh, Lars (author)
- Karolinska Institutet,Department of Clinical Science and Education, Karolinska Institutet Södersjukhuset, Stockholm, Sweden
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- Agardh, Daniel (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden
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- Wahlström, Jan, 1939 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,University of Gothenburg,Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
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- Nilsson, Staffan, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg,Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden
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- Torinsson Naluai, Åsa, 1968 (author)
- Högskolan i Skövde,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,University of Gothenburg,Institutionen för vård och natur,Forskningscentrum för Systembiologi,Institute of Biomedicine, Department of Medical and Clinical Genetics, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
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(creator_code:org_t)
- 2013-08-02
- 2013
- English.
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Abstract
Subject headings
Close
- Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other chronic disorders with an inflammatory component.
Subject headings
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- COMPLEX HUMAN-DISEASES
- TISSUE TRANSGLUTAMINASE
- RISK VARIANTS
- STRESS
- APPL1
- MAPK
- DISEQUILIBRIUM
- PHOSPHATASE
- METABOLISM
- ACTIVATION
- COMPLEX HUMAN-DISEASES
- Natural sciences
Publication and Content Type
- ref (subject category)
- art (subject category)
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Östensson, Malin ...
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Montén, Caroline
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Bacelis, Jonas, ...
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Gudjonsdottir, A ...
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Adamovic, Svetla ...
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Ek, Johan
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Ascher, Henry, 1 ...
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Pollak, Elisabet
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Arnell, Henrik
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Browaldh, Lars
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Agardh, Daniel
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Wahlström, Jan, ...
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Nilsson, Staffan ...
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Torinsson Naluai ...
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and Biological Scien ...
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and Pediatrics
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MEDICAL AND HEAL ...
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and Endocrinology an ...
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MEDICAL AND HEAL ...
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University of Gothenburg
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Chalmers University of Technology
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Lund University
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Karolinska Institutet
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University of Skövde