Inviting an author to review:
Find an author and click ‘Invite to review selected article’ near their name.
Search for authorsSearch for similar articles
292
views
0
recommends
+1 Recommend
0 collections
    20
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Multiple common variants for celiac disease influencing immune gene expression

      research-article
      1 , 2 , 1 , 2 , 1 , 2 , 3 , 4 , 1 , 5 , 6 , 7 , 8 , 9 , 1 , 10 , 10 , 2 , 10 , 5 , 11 , 12 , 13 , 14 , 15 , 16 , 15 , 17 , 18 , 19 , 20 , 17 , 21 , 17 , 22 , 15 , 23 , 3 , 13 , 1 , 22 , 15 , 24 , 25 , 10 , 2 , 26 , 27 , 28 , 15 , 29 , 2 , 30 , 6 , 23 , 31 , 24 , 18 , 9 , 24 , 2 , 32 , 16 , 10 , 33 , 31 , 34 , 18 , 35 , 15 , 15 , 36 , 2 , 1
      Nature genetics

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          We performed a second-generation genome wide association study of 4,533 celiac disease cases and 10,750 controls. We genotyped 113 selected SNPs with P GWAS<10 −4, and 18 SNPs from 14 known loci, in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome wide significance ( P combined<5×10 −8), most contain immune function genes ( BACH2, CCR4, CD80, CIITA/ SOCS1/ CLEC16A, ICOSLG, ZMIZ1) with ETS1, RUNX3, THEMIS and TNFRSF14 playing key roles in thymic T cell selection. A further 13 regions had suggestive association evidence. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated ( P<0.0028, FDR 5%) with cis gene expression.

          Related collections

          Most cited references31

          • Record: found
          • Abstract: found
          • Article: not found

          Singular value decomposition for genome-wide expression data processing and modeling.

          We describe the use of singular value decomposition in transforming genome-wide expression data from genes x arrays space to reduced diagonalized "eigengenes" x "eigenarrays" space, where the eigengenes (or eigenarrays) are unique orthonormal superpositions of the genes (or arrays). Normalizing the data by filtering out the eigengenes (and eigenarrays) that are inferred to represent noise or experimental artifacts enables meaningful comparison of the expression of different genes across different arrays in different experiments. Sorting the data according to the eigengenes and eigenarrays gives a global picture of the dynamics of gene expression, in which individual genes and arrays appear to be classified into groups of similar regulation and function, or similar cellular state and biological phenotype, respectively. After normalization and sorting, the significant eigengenes and eigenarrays can be associated with observed genome-wide effects of regulators, or with measured samples, in which these regulators are overactive or underactive, respectively.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Searching for genetic determinants in the new millennium.

            N Risch (2000)
            Human genetics is now at a critical juncture. The molecular methods used successfully to identify the genes underlying rare mendelian syndromes are failing to find the numerous genes causing more common, familial, non-mendelian diseases. With the human genome sequence nearing completion, new opportunities are being presented for unravelling the complex genetic basis of non-mendelian disorders based on large-scale genome-wide studies. Considerable debate has arisen regarding the best approach to take. In this review I discuss these issues, together with suggestions for optimal post-genome strategies.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Shared and distinct genetic variants in type 1 diabetes and celiac disease.

              Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared. We evaluated the association between type 1 diabetes and eight loci related to the risk of celiac disease by genotyping and statistical analyses of DNA samples from 8064 patients with type 1 diabetes, 9339 control subjects, and 2828 families providing 3064 parent-child trios (consisting of an affected child and both biologic parents). We also investigated 18 loci associated with type 1 diabetes in 2560 patients with celiac disease and 9339 control subjects. Three celiac disease loci--RGS1 on chromosome 1q31, IL18RAP on chromosome 2q12, and TAGAP on chromosome 6q25--were associated with type 1 diabetes (P<1.00x10(-4)). The 32-bp insertion-deletion variant on chromosome 3p21 was newly identified as a type 1 diabetes locus (P=1.81x10(-8)) and was also associated with celiac disease, along with PTPN2 on chromosome 18p11 and CTLA4 on chromosome 2q33, bringing the total number of loci with evidence of a shared association to seven, including SH2B3 on chromosome 12q24. The effects of the IL18RAP and TAGAP alleles confer protection in type 1 diabetes and susceptibility in celiac disease. Loci with distinct effects in the two diseases included INS on chromosome 11p15, IL2RA on chromosome 10p15, and PTPN22 on chromosome 1p13 in type 1 diabetes and IL12A on 3q25 and LPP on 3q28 in celiac disease. A genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles. These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases. 2008 Massachusetts Medical Society
                Bookmark

                Author and article information

                Journal
                9216904
                2419
                Nat Genet
                Nat. Genet.
                Nature genetics
                1061-4036
                1546-1718
                8 February 2010
                28 February 2010
                April 2010
                01 October 2010
                : 42
                : 4
                : 295-302
                Affiliations
                [1 ]Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
                [2 ]Genetics Department, University Medical Center and Groningen University, 9700 RB Groningen, The Netherlands
                [3 ]The Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
                [4 ]Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
                [5 ]Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary
                [6 ]National Institute for Health and Welfare, Helsinki 00271, Finland
                [7 ]Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
                [8 ]Department of Medical Sciences, University of Milan, Italy
                [9 ]Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Heidelbergaan 100, Utrecht, The Netherlands
                [10 ]Clinical Immunology Department, Hospital Clínico San Carlos, Madrid, Spain
                [11 ]Public Health Research Group of Hungarian Academy of Sciences, Medical & Health Science Center, University of Debrecen, Debrecen, Hungary
                [12 ]Unita’ di Aterosclerosi e Trombosi, I.R.C.C.S Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Foggia, Italy
                [13 ]NIHR GSTFT/KCL Comprehensive Biomedical Research Centre King’s College London School of Medicine 7th Floor Tower Wing Guy’s Hospital London SE19RT United Kingdom
                [14 ]Dept. of Pulmonology, University Medical Center and Groningen University, 9700 RB Groningen, The Netherlands
                [15 ]Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
                [16 ]Department of Paediatric Gastroenterology, University Medical Centre Utrecht, Utrecht, The Netherlands
                [17 ]Paediatric Research Centre, University of Tampere Medical School and Tampere University Hospital, Tampere, Finland
                [18 ]Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland
                [19 ]Heim Pal Childrens Hospital, Budapest, Hungary
                [20 ]Department of Pediatrics, Medical and Health Science Center, University of Debrecen, Hungary
                [21 ]Gastrointestinal Unit, Mater Misericordiae University Hospital, Eccles St., Dublin 7, Ireland
                [22 ]Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
                [23 ]Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands
                [24 ]Department of Gastroenterology, VU Medical Center, 1007 MB Amsterdam, The Netherlands
                [25 ]Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
                [26 ]Department of Medical Genetics and Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, The Netherlands
                [27 ]Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA
                [28 ]Pediatric Gastroenterology Department, Hospital La Paz, Madrid, Spain
                [29 ]Institute for Molecular Medicine Finland, FIMM, Helsinki 00290, Finland
                [30 ]Department of Gastroenterology, Hepatology and Immunology, Children’s Memorial Health Institute, Warsaw, Poland
                [31 ]European Laboratory for Food Induced Disease, University of Naples Federico II, Naples, Italy
                [32 ]Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
                [33 ]Department of Pathology, Children’s Memorial Health Institute, Warsaw, Poland
                [34 ]Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, USA
                [35 ]Department of Experimental Medicine, Faculty of Medicine University of Milano-Bicocca, Monza, Italy
                [36 ]Department of Medical Genetics & Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
                Author notes
                Correspondence to DAvH ( d.vanheel@ 123456qmul.ac.uk ) or regarding expression analyses to LF ( lude@ 123456ludesign.nl ).
                [37]

                These authors contributed equally

                AUTHOR CONTRIBUTION STATEMENT

                DAvH and CW designed, co-ordinated and led the study. Experiments were performed in the labs of CW, DAvH, CAM, PD and PMG. Major contributions were: 1) DNA sample preparation - PCAD, GT, KAH, JR, AZ, PS 2) genotyping - PCAD, GT, KAH, AC, JR, RG; 3) expression data generation - HJMG, LHvdB, RAO, RKW, LF; 4) case/control association analyses - PCAD, GT, LF, JCB, DAvH; 5) expression analyses - LF, GAH, RSNF; 6) manuscript preparation - PCAD, GT, LF, RSNF, GAH, JCB, CW, DAvH. Other authors contributed variously to sample collection and all other aspects of the study. All authors reviewed the final manuscript.

                Article
                UKMS28740
                10.1038/ng.543
                2847618
                20190752
                81e9ac37-9bf8-446f-a35b-aec4c01450df

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: Wellcome Trust :
                Award ID: 084743 || WT
                Funded by: Medical Research Council :
                Award ID: G0700545(82277) || MRC_
                Categories
                Article

                Genetics
                Genetics

                Comments

                Comment on this article