Genomes and Genes
John D Rioux
Affiliation: Massachusetts Institute of Technology
- Paths to understanding the genetic basis of autoimmune diseaseJohn D Rioux
1 Inflammatory Disease Research, The Broad Institute of MIT and Harvard, Harvard Medical School, Brigham and Women s Hospital, 1 Kendall Square, Building 300, Cambridge, Massachusetts 02139 1561, USA
Nature 435:584-9. 2005....
- Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitisAlexandra Chloe Villani
Department of Gastroenterology, McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada
PLoS ONE 4:e7154. 2009..The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene...
- Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesisJohn D Rioux
Université de Montréal and the Montreal Heart Institute, Research Center, 5000 rue Belanger, Montreal, Quebec H1T 1C8, Canada
Nat Genet 39:596-604. 2007..Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease...
- Genomewide search and association studies in a Finnish celiac disease population: Identification of a novel locus and replication of the HLA and CTLA4 lociJohn D Rioux
Broad Institute Massachusetts Institute of Technology, One Kendall Square, Bldg 300, Cambridge, MA 02139 1561, USA
Am J Med Genet A 130:345-50. 2004..We also performed targeted typing and analyses that replicated the associations of the HLA and CTLA4 loci...
- Evaluating the role of the 620W allele of protein tyrosine phosphatase PTPN22 in Crohn's disease and multiple sclerosisPhilip L De Jager
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
Eur J Hum Genet 14:317-21. 2006....
- Risk alleles for multiple sclerosis identified by a genomewide studyDavid A Hafler
Division of Molecular Immunology, Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, and Harvard Medical School, Boston, USA
N Engl J Med 357:851-62. 2007..Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis...
- Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19Marcela Karey Tello-Ruiz
The Broad Institute of MIT and Harvard, Cambridge, MA, USA
Eur J Hum Genet 14:780-90. 2006..Overall, we performed the most comprehensive candidate-gene association study for IBD to date. The information hereby generated constitutes a valuable resource to investigate other common genetic immune diseases, such as celiac disease...
- Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseasesJohn D Rioux
Research Center, Université de Montréal and Montreal Heart Institute, Montreal, QC, Canada
Proc Natl Acad Sci U S A 106:18680-5. 2009..The data demonstrate that MHC associations with autoimmune diseases result from complex, multilocus effects that span the entire region...
- Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitisMelissa Beaudoin
Montreal Heart Institute, Research Center, Montreal, Quebec, Canada
PLoS Genet 9:e1003723. 2013..Rather, these are expected to help focus functional studies of the corresponding disease loci...
- Association of DLG5 R30Q variant with inflammatory bowel diseaseMark J Daly
The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA
Eur J Hum Genet 13:835-9. 2005..This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect...
- Pooled DNA resequencing of 68 myocardial infarction candidate genes in French canadiansMelissa Beaudoin
Montreal Heart Institute, 5000 rue Belanger, Montreal, Quebec, Canada
Circ Cardiovasc Genet 5:547-54. 2012..Except for a few examples (eg, PCSK9), the role of low-frequency genetic variation (minor allele frequency [MAF]) ≈0.1%-5% on MI/coronary artery disease predisposition has not been extensively investigated...
- Genome-wide expression profiling implicates a MAST3-regulated gene set in colonic mucosal inflammation of ulcerative colitis patientsCatherine Labbe
Institut de Cardiologie de Montreal, Montreal, Quebec, Canada
Inflamm Bowel Dis 18:1072-80. 2012..Testing MAST3 in a reporter assay provided preliminary evidence that MAST3 modulates the activity of inflammation-related transcription factor nuclear factor kappa B...
- Common variants in the NLRP3 region contribute to Crohn's disease susceptibilityAlexandra Chloe Villani
Division of Gastroenterology, McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada
Nat Genet 41:71-6. 2009..Mutations in NLRP3 are known to be responsible for three rare autoinflammatory disorders. These results suggest that the NLRP3 region is also implicated in the susceptibility of more common inflammatory diseases such as Crohn's disease...
- A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHCPaul I W de Bakker
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Genet 38:1166-72. 2006....
- Identification of a chromosome 8p locus for early-onset coronary heart disease in a French Canadian populationJames C Engert
McGill University Health Centre, Montreal, Quebec, Canada
Eur J Hum Genet 16:105-14. 2008..In conclusion, a genome-wide scan and additional fine mapping provide evidence for a locus on chromosome 8 that contributes to CHD in a French Canadian population...
- LRRK2 is involved in the IFN-gamma response and host response to pathogensAgnès Gardet
Center for the Study of the Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
J Immunol 185:5577-85. 2010..These observations indicate that LRRK2 is an IFN-γ target gene, and it might be involved in signaling pathways relevant to Crohn's disease pathogenesis...
- Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4Robert M Plenge
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Am J Hum Genet 77:1044-60. 2005....
- Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's diseaseSteven A McCarroll
Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Nat Genet 40:1107-12. 2008..These results suggest that the CD association at IRGM arises from an alteration in IRGM regulation that affects the efficacy of autophagy and identify a common deletion polymorphism as a likely causal variant...
- Molecular pathogenesis of inflammatory bowel disease: genotypes, phenotypes and personalized medicinePhilippe Goyette
Universite de Montreal, Department of Medicine, Montreal, Quebec, Canada
Ann Med 39:177-99. 2007..Moreover, these approaches and tools can be applied in the context of variable drug response with the goal of providing more personalized clinical management of patients with IBD...
- Autoimmune diseases: insights from genome-wide association studiesGuillaume Lettre
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Hum Mol Genet 17:R116-21. 2008..Finally, we open a discussion on ways to best maximize the impact of these genetic discoveries where it matters the most, that is for autoimmune disease patients...
- Genome-wide association studies: a new window into immune-mediated diseasesRamnik J Xavier
Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Nat Rev Immunol 8:631-43. 2008..Although much work remains to be done, in this Review we discuss what effect these studies are having on our understanding of disease pathogenesis and their potential impact on future immunology studies...
- Autophagy as an important process in gut homeostasis and Crohn's disease pathogenesisRamnik J Xavier
Université de Montréal and the Montreal Heart Institute, Research Center, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada
Gut 57:717-20. 2008
- A functional candidate screen for coeliac disease genesChristine R Curley
The Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA
Eur J Hum Genet 14:1215-22. 2006..The findings in coeliac disease need to be replicated. Expanding genetic association studies of these cytochrome genes to other inflammatory conditions should reveal whether their causative influence extends beyond coeliac disease...
- Progress towards identifying inflammatory bowel disease susceptibility genesJohn D Rioux
Inflammatory Disease Research, Broad Institute of MIT and Harvard, Brigham and Women s Hospital, Harvard Medical School, Cambridge, MA 02139 1561, USA
Novartis Found Symp 263:3-11; discussion 11-6, 211-8. 2004..gene or genetic variant? (3) How can we best use this information to obtain an understanding of the biological mechanisms underlying disease susceptibility and to identify useful markers of disease progression and response to therapy?..
- T-bet polymorphisms are associated with asthma and airway hyperresponsivenessBenjamin A Raby
M D C M, Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
Am J Respir Crit Care Med 173:64-70. 2006..Little is known regarding the role of genetic variation surrounding T-bet in the development of human AHR...
- Genetic analysis of multiple sclerosisEmily C Walsh
Whitehead Institute for Biomedical Research, Center for Genome Research, One Kendall Square, Cambridge, MA 02141, USA
J Autoimmun 21:111-6. 2003..Lastly, we review recent important advances in our understanding of the patterns of genetic variation in the human genome and speculate about how these advances will aid in future studies of the genetic causes of MS...
- Genome scan analyses and positional cloning strategy in IBD: successes and limitationsGary E Wild
Inflammatory Disease Research Group, Human Medical and Population Genetics, Whitehead Institute MIT Center for Genome Research, One Kendall Square, Bldg 300, Cambridge, MA 02139 1561, USA
Best Pract Res Clin Gastroenterol 18:541-53. 2004..Although many issues related to the function and expression of these genes await elucidation, there is a shared optimism that pivotal clinical applications will emerge from these investigations...
- Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosusRobert R Graham
Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA
Nat Genet 40:1059-61. 2008..These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA...
- Role of the IBD5 susceptibility locus in the inflammatory bowel diseasesClaudia Reinhard
Montreal Heart Institute, Universite de Montreal, Montreal, Canada
Inflamm Bowel Dis 12:227-38. 2006..In addition, we discuss the challenges faced when the region identified by association contains multiple genes that are not easily separated by recombination-the primary tool of the human geneticist...
- CARD15 genetic variation in a Quebec population: prevalence, genotype-phenotype relationship, and haplotype structureSeverine Vermeire
Department of Gastroenterology, McGill University Health Centre, McGill University, Montreal, Canada
Am J Hum Genet 71:74-83. 2002..This structure helps clarify the history of these causal mutations. Finally, this analysis shows that CARD15 involvement with CD is detectable by use of publicly available SNPs alone...
- GWA studies: rewriting the story of IBDMarcia L Budarf
Université de Montréal and the Montreal Heart Institute, Research Center, 5000 rue Belanger, Montreal, Quebec H1T 1C8, Canada
Trends Genet 25:137-46. 2009..In this review, we discuss how GWA studies are enabling us to rewrite the story of IBD pathogenesis, focusing on the interleukin-23 and autophagy pathways...
- New approaches to gene hunting in IBDMark J Daly
Whitehead Institute MIT Center for Genome Research, Cambridge, MA, USA
Inflamm Bowel Dis 10:312-7. 2004..Along the way we highlight the successful work by many groups in studying the genetics of IBD, where significant successes have arrived earlier than in most other complex human diseases...
- Identifying susceptibility genes for immunological disorders: patterns, power, and proofRobert Plenge
Division of Rheumatology, Immunology and Allergy, Brigham and Women s Hospital, Boston, MA, USA
Immunol Rev 210:40-51. 2006..Recent developments in the fields of human genetics and genomics are overcoming limitations within the field, and we anticipate many exciting discoveries in the near future...
- An integrated haplotype map of the human major histocompatibility complexEmily C Walsh
Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA
Am J Hum Genet 73:580-90. 2003..Furthermore, these data show that multi-SNP haplotypes will likely be a valuable means for refining association signals in this region...
- Genetic variation in toll-like receptor 9 and susceptibility to systemic lupus erythematosusPhilip L De Jager
Department of Neurology, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
Arthritis Rheum 54:1279-82. 2006..This variability in activation threshold may, in turn, affect an individual's susceptibility to SLE. This study assessed the role of genetic variation within the TLR-9 gene in susceptibility to SLE...
- Optimus Primer: A PCR enrichment primer design program for next-generation sequencing of human exonic regionsAndrew Mk Brown
Universite de Montreal, Montreal, Quebec, Canada
BMC Res Notes 3:185. 2010....
- IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitisCosmas Giallourakis
Center for Genome Research, Whitehead Institute, One Kendall Square, Bldg 300, Cambridge, MA 02139, USA
Am J Hum Genet 73:205-11. 2003..Taken together, our results suggest that IBD5 may act as a general risk factor for IBD, with loci such as CARD15 modifying the clinical characteristics of disease...
- ATG16L1 and IL23R are associated with inflammatory bowel diseases but not with celiac disease in the NetherlandsRinse K Weersma
Department of Gastroenterology and Hepatology, University Medical Center Groningen, The Netherlands
Am J Gastroenterol 103:621-7. 2008..We performed a case-control study for the association of IBD with IL23R and ATG16L1 in a Dutch cohort. We also looked at the association of IL23R and ATG16L1 with celiac disease...
- Identification of two independent risk factors for lupus within the MHC in United Kingdom familiesMichelle M A Fernando
Section of Molecular Genetics and Rheumatology, Imperial College London, London, United Kingdom
PLoS Genet 3:e192. 2007..Our class III signal importantly excludes independent association at the TNF promoter polymorphism, TNF-308G/A, in our SLE cohort and provides a potentially novel locus for future genetic and functional studies...
- Evidence of transmission ratio distortion of DLG5 R30Q variant in general and implication of an association with Crohn disease in menFrauke Friedrichs
Leibniz Institute for Arteriosclerosis Research, Domagkstr 3, 48149, Muenster, Germany
Hum Genet 119:305-11. 2006....
- Direct or indirect association in a complex disease: the role of SLC22A4 and SLC22A5 functional variants in Crohn diseaseSheila A Fisher
Department of Medical and Molecular Genetics, King s College London School of Medicine, Guy s Hospital, London, United Kingdom
Hum Mutat 27:778-85. 2006....
- Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's diseaseMark S Silverberg
Department of Medicine, Mount Sinai Hospital IBD Centre, University of Toronto, Toronto, Ontario, Canada
Eur J Hum Genet 15:328-35. 2007....
- Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's diseaseJeffrey C Barrett
Bioinformatics and Statistical Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Nat Genet 40:955-62. 2008..The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development...
- A genome-wide association study identifies IL23R as an inflammatory bowel disease geneRichard H Duerr
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian, Mezzanine Level, C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA
Science 314:1461-3. 2006..These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease...
- A high-resolution linkage-disequilibrium map of the human major histocompatibility complex and first generation of tag single-nucleotide polymorphismsMarcos M Miretti
Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Am J Hum Genet 76:634-46. 2005..This LD map allowed us to give coordinates for the extremely variable LD structure underlying the MHC...
- Haplotype structure of TNFRSF5-TNFSF5 (CD40-CD40L) and association analysis in systemic lupus erythematosusSapna Chadha
Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK
Eur J Hum Genet 13:669-76. 2005..Haplotype tagging SNPs (htSNPs) are made known, which will facilitate analysis for susceptibility in other autoimmune diseases and risk for infectious disease...
- Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohortGeoffrey C Nguyen
Harvey M and Lyn P Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Am J Gastroenterol 101:1012-23. 2006..This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population...
- Re: GAMES issue study: Are international genetic consortia functional?Philip L De Jager
J Neuroimmunol 153:5-6. 2004
- Enhancing linkage analysis of complex disorders: an evaluation of high-density genotypingStephen J Sawcer
University of Cambridge Neurology Unit, Addenbrooke s Hospital, UK
Hum Mol Genet 13:1943-9. 2004..The extent of additional information extracted is considerable, indicating that reanalysis of existing multiplex families using these newer systems would substantially increase power...
- Inflammatory bowel disease susceptibility loci defined by genome scan meta-analysis of 1952 affected relative pairsDavid A van Heel
Department of Gastoenterology, Imperial College London, UK
Hum Mol Genet 13:763-70. 2004..Clustering of adjacent bins was observed for chromosomes 6p, 16, 19p. The meta-analysis has identified novel loci and prioritized genomic regions for further gene identification studies...
- Using a genome-wide scan and meta-analysis to identify a novel IBD locus and confirm previously identified IBD lociC Noel Williams
Queen Elizabeth II Health Sciences Center University Hospital, Nova Scotia, Canada
Inflamm Bowel Dis 8:375-81. 2002..Meta-analysis of linkage data is a powerful approach for identifying and confirming common susceptibility loci and specifically shows that, and are the major, common IBD susceptibility loci in the populations studied thus far...
- Mapping autoimmune disease genes in humans: lessons from IBD and SLETimothy J Vyse
Rheumatology Section, Imperial College of London, Faculty of Medicine, Hammersmith Hospital, London W12 0NN, UK
Novartis Found Symp 267:94-107; discussion 107-12. 2005..We will examine how some of the recent advances in our understanding of genetic variation in the human genome are greatly improving our ability to map autoimmune disease genes in humans...
- Association analysis of the R620W polymorphism of protein tyrosine phosphatase PTPN22 in systemic lupus erythematosus families: increased T allele frequency in systemic lupus erythematosus patients with autoimmune thyroid diseaseHui Wu
David Geffen School of Medicine, University of California, Los Angeles, 90095, USA
Arthritis Rheum 52:2396-402. 2005..We performed family-based association studies of this polymorphism in 4 independent cohorts containing SLE patients and their parents and/or other family members...
- Genetic variation in myosin IXB is associated with ulcerative colitisAdriaan A van Bodegraven
Department of Gastroenterology, VU University Medical Centre, Amsterdam, The Netherlands
Gastroenterology 131:1768-74. 2006..These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease...
- A second major histocompatibility complex susceptibility locus for multiple sclerosisTai Wai Yeo
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
Ann Neurol 61:228-36. 2007..The possibility that other genes in the MHC independently influence susceptibility to multiple sclerosis has been suggested but remains unconfirmed...
- Prevalence of CARD15/NOD2 mutations in Caucasian healthy peopleJean Pierre Hugot
INSERM Avenir U763 AP HP Université Paris 7, Hopital Robert Debre, Paris, France
Am J Gastroenterol 102:1259-67. 2007..This high risk may support the opinion that CARD15/NOD2 variants are strong CD risk factors at the individual and population levels...
- Assessment of reliability and validity of IBD phenotyping within the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium (IBDGC)Themistocles Dassopoulos
Johns Hopkins University Meyerhoff Inflammatory Bowel Disease Center, Baltimore MD, USA
Inflamm Bowel Dis 13:975-83. 2007..Our aim was to determine the reliability and validity of these phenotypic assessments...
- Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locusJean Paul Achkar
Center for Inflammatory Bowel Disease, Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, OH, USA
Am J Gastroenterol 101:572-80. 2006..The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci...
- Understanding association and causality in the genetic studies of inflammatory bowel diseaseTruc T Trinh
Gastroenterology 129:2106-10. 2005
- Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosusDeborah S Cunninghame Graham
Section of Molecular Genetics and Rheumatology, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
Nat Genet 40:83-9. 2008..We hypothesize that increased expression of TNFSF4 predisposes to SLE either by quantitatively augmenting T cell-APC interaction or by influencing the functional consequences of T cell activation via TNFRSF4...
- Haplotype analysis of tumour necrosis factor receptor genes in 1p36: no evidence for association with systemic lupus erythematosusSapna Chadha
Rheumatology Section, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK
Eur J Hum Genet 14:69-78. 2006..Haplotype tagging SNPs are made known across areas of strong LD, which will facilitate analysis for susceptibility in other diseases...
- A high-density screen for linkage in multiple sclerosisStephen Sawcer
University of Cambridge, Department of Clinical Neuroscience, Addenbrooke s Hospital, Hills Road, Cambridge, CB2 2QQ, United Kingdom
Am J Hum Genet 77:454-67. 2005....
- Defining the role of the MHC in autoimmunity: a review and pooled analysisMichelle M A Fernando
Section of Molecular Genetics and Rheumatology, Faculty of Medicine, Imperial College London, London, United Kingdom
PLoS Genet 4:e1000024. 2008..Furthermore, we find a number of interesting commonalities and differences across diseases that implicate both general and disease-specific pathogenetic mechanisms in autoimmunity...
- Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other lociJohn B Harley
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104, USA
Nat Genet 40:204-10. 2008..Our results show that numerous genes, some with known immune-related functions, predispose to SLE...