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DOI 10.1038/ng.2614

Медицинская библиотека · Nature genetics · 2013

Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.

Hinks Anne, Cobb Joanna, Marion Miranda C, Prahalad Sampath, Sudman Marc, Bowes John, Martin Paul, Comeau Mary E, Sajuthi Satria, Andrews Robert, Brown Milton, Chen Wei-Min, Concannon Patrick, Deloukas Panos, Edkins Sarah, Eyre Stephen, Gaffney Patrick M, Guthery Stephen L, Guthridge Joel M, Hunt Sarah E, James Judith A, Keddache Mehdi, Moser Kathy L, Nigrovic Peter A, Onengut-Gumuscu Suna, Onslow Mitchell L, Rosé Carlos D, Rich Stephen S, Steel Kathryn J A, Wakeland Edward K, Wallace Carol A, Wedderburn Lucy R, Woo Patricia, Boston Children's JIA Registry, British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group, Childhood Arthritis Prospective Study (CAPS), Childhood Arthritis Response to Medication Study (CHARMS), German Society for Pediatric Rheumatology (GKJR), JIA Gene Expression Study, NIAMS JIA Genetic Registry, TREAT Study, United Kingdom Juvenile Idiopathic Arthritis Genetics Consortium (UKJIAGC), Bohnsack John F, Haas Johannes Peter, Glass David N, Langefeld Carl D, Thomson Wendy, Thompson Susan D

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

We used the Immunochip array to analyze 2,816 individuals with juvenile idiopathic arthritis (JIA), comprising the most common subtypes (oligoarticular and rheumatoid factor-negative polyarticular JIA), and 13,056 controls. We confirmed association of 3 known JIA risk loci (the human leukocyte antigen (HLA) region, PTPN22 and PTPN2) and identified 14 loci reaching genome-wide significance (P < 5 × 10(-8)) for the first time. Eleven additional new regions showed suggestive evidence of association with JIA (P < 1 × 10(-6)). Dense mapping of loci along with bioinformatics analysis refined the associations to one gene in each of eight regions, highlighting crucial pathways, including the interleukin (IL)-2 pathway, in JIA disease pathogenesis. The entire Immunochip content, the HLA region and the top 27 loci (P < 1 × 10(-6)) explain an estimated 18, 13 and 6% of the risk of JIA, respectively. In summary, this is the largest collection of JIA cases investigated so far and provides new insight into the genetic basis of this childhood autoimmune disease.

Для цитирования: Hinks Anne, Cobb Joanna, Marion Miranda C, Prahalad Sampath, Sudman Marc, Bowes John, Martin Paul, Comeau Mary E, Sajuthi Satria, Andrews Robert, Brown Milton, Chen Wei-Min, Concannon Patrick, Deloukas Panos, Edkins Sarah, Eyre Stephen, Gaffney Patrick M, Guthery Stephen L, Guthridge Joel M, Hunt Sarah E, James Judith A, Keddache Mehdi, Moser Kathy L, Nigrovic Peter A, Onengut-Gumuscu Suna, Onslow Mitchell L, Rosé Carlos D, Rich Stephen S, Steel Kathryn J A, Wakeland Edward K, Wallace Carol A, Wedderburn Lucy R, Woo Patricia, Boston Children's JIA Registry, British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group, Childhood Arthritis Prospective Study (CAPS), Childhood Arthritis Response to Medication Study (CHARMS), German Society for Pediatric Rheumatology (GKJR), JIA Gene Expression Study, NIAMS JIA Genetic Registry, TREAT Study, United Kingdom Juvenile Idiopathic Arthritis Genetics Consortium (UKJIAGC), Bohnsack John F, Haas Johannes Peter, Glass David N, Langefeld Carl D, Thomson Wendy, Thompson Susan D. Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis.. Nature genetics. 2013. DOI: 10.1038/ng.2614.

Предметные рубрики MeSH

AdultArthritis, JuvenileCase-Control StudiesChildChromosome MappingGene FrequencyGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansInterleukinsLinkage DisequilibriumMolecular Sequence AnnotationPolymorphism, Single NucleotideReceptors, CCRReceptors, InterleukinRisk Factors
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