SynthesisNature medicine2015
Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.
Open access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 9 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
156citing papers in PubMed, 9 pooled it
10.2field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
156 citing papers in PubMed, 9 syntheses or guidelines pooled it, 283 citations in OpenAlex.
- Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency.Clinical immunology (Orlando, Fla.) · 2024Pooled it
- PheWAS and cross-disorder analysis reveal genetic architecture, pleiotropic loci and phenotypic correlations across 11 autoimmune disorders.Frontiers in immunology · 2023Pooled it
- Genome-wide association analysis of adaptation to oxygen stress in Nile tilapia (Oreochromis niloticus).BMC genomics · 2021Pooled it
- Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology.Nature communications · 2021Pooled it
- Genome-wide meta-analysis reveals shared newAnnals of the rheumatic diseases · 2019Pooled it
- Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations.Genome medicine · 2018Pooled it
- Pooled it
- Copy number variation meta-analysis reveals a novel duplication at 9p24 associated with multiple neurodevelopmental disorders.Genome medicine · 2017Pooled it
- Pooled it
- Tie2 protects the vasculature against thrombus formation in systemic inflammation.The Journal of clinical investigation · 2018Trial
- Gut-reproduction axis: genome-wide pleiotropic and prospective evidence linking inflammatory bowel disease with gynecological disorders.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Genetic Contribution to Asthma Informs Acute Chest Syndrome Pathophysiology and Risk Stratification.American journal of hematology · 2026Article
- Using Importance Sampling to EstimateArXiv · 2026Article
- Tonsillar expression quantitative trait loci verify and expand genetic contributors to childhood atopic diseases.bioRxiv : the preprint server for biology · 2026Article
- Heterogeneity in the association of genetic risk for RA and resultant RA phenotypes.Rheumatology (Oxford, England) · 2026Article
- [XVII Post-ECTRIMS Meeting: Review of the New Developments Presented at the 2024 ECTRIMS Congress (I)].Revista de neurologia · 2026Review
- RWDisEnh+: Enhancing disease-enhancer association prediction through multiplex-heterogeneous networks.PloS one · 2026Article
- Rare and common variants in ERAP1 and ERAP2 selected for in response to Yersinia pestis infection contribute to autoimmune disease including inflammatory bowel disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Exploring the genetic architecture of multiple long-term conditions using a genome-wide association study in the UK Biobank population.Scientific reports · 2025Article
- Development and External Validation of a Genetic Risk Score for Pain in Rheumatoid Arthritis.Arthritis care & research · 2025Article
96 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
66 authors at 20 institutions in 6 countries.
Yun R LiThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.ORCID http://orcid.org/0000-0002-8077-4975
Jin LiThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Sihai D ZhaoDepartment of Biostatistics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jonathan P BradfieldThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Frank D MentchThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
S Melkorka MaggadottirThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Cuiping HouThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Debra J AbramsThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Diana ChangDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA.
Feng GaoDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA.
Yiran GuoThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.ORCID http://orcid.org/0000-0002-6549-8589
Zhi WeiDepartment of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, USA.
John J ConnollyThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Christopher J CardinaleThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Marina BakayThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Joseph T GlessnerThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Dong LiThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Charlly KaoThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Kelly A ThomasThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.ORCID http://orcid.org/0000-0002-9719-2664
Haijun QiuThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Rosetta M ChiavacciThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Cecilia E KimThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Fengxiang WangThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
James SnyderThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Marylyn D RichieDepartment of Biochemistry and Molecular Biology, Eberly College of Science, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.
Berit FlatøDepartment of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Øystein FørreDepartment of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Lee A DensonDivision of Gastroenterology, The Center for Inflammatory Bowel Disease, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Susan D ThompsonDivison of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Mara L BeckerDivision of Rheumatology, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
Stephen L GutheryDepartment of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah, USA.
Anna LatianoDivision of Gastroenterology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Elena PerezDivision of Pediatric Allergy and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Elena ResnickInstitute of Immunology and Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA.
Richard K RussellDepartment of Paediatric Gastroenterology, Yorkhill Hospital for Sick Children, Glasgow, Scotland, UK.
David C WilsonPaediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, University of Edinburgh, Ediburgh, UK.
Mark S SilverbergMount Sinai Hospital IBD Centre, University of Toronto, Toronto, Ontario, Canada.
Vito AnneseUnit of Gastroenterology, Department of Medical and Surgical Specialties, Careggi University Hospital, Florence, Italy.
Benedicte A LieDepartment of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Marilynn PunaroDepartment of Rheumatology, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA.
Marla C DubinskyDepartment of Pediatrics, Pediatric IBD Center, Cedars Sinai Medical Center, Los Angeles, California, USA.
Dimitri S MonosDepartment of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Caterina StrisciuglioDepartment of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
Annamaria StaianoDepartment of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
Erasmo MieleDepartment of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
Subra KugathasanDepartment of Pediatrics, Emory University School of Medicine and Children's Health Care of Atlanta, Atlanta, Georgia, USA.
Justine A EllisGenes, Environment and Complex Disease, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Jane E MunroPediatric Rheumatology Unit, Royal Children's Hospital, Parkville, Victoria, Australia.
Kathleen E SullivanDivision of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Carol A WiseSarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA.
Helen ChapelDepartment of Clinical Immunology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Charlotte Cunningham-RundlesInstitute of Immunology and Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA.
Struan F A GrantThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Jordan S OrangeSection of Immunology, Allergy, and Rheumatology, Department of Pediatric Medicine, Texas Children's Hospital, Houston, Texas, USA.
Patrick M A SleimanThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Edward M BehrensDepartment of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Anne M GriffithsThe Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Jack SatsangiGastrointestinal Unit, Division of Medical Sciences, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK.
Terri H FinkelDepartment of Pediatrics, Nemours Children's Hospital, Orlando, Florida, USA.
Alon KeinanDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA.
Eline T Luning PrakDepartment of Pathology and Lab Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Constantin PolychronakosDepartments of Pediatrics and Human Genetics, McGill University Health Centre Research Institute, Montréal, Québec, Canada.
Robert N BaldassanoDepartment of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Hongzhe LiDepartment of Pathology and Lab Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Brendan J KeatingThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Hakon HakonarsonThe Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Children's Hospital of Philadelphia · USCornell University · USOslo University Hospital · NOUniversity of Naples Federico II · ITUniversity of Pennsylvania · USCincinnati Children's Hospital Medical Center · USIcahn School of Medicine at Mount Sinai · USTexas Scottish Rite Hospital for Children · USAzienda Ospedaliero-Universitaria Careggi · ITCasa Sollievo della Sofferenza · ITCedars-Sinai Medical Center · USChildren's Mercy Hospital · USEmory University · USMcGill University Health Centre · CAMount Sinai Hospital · CANemours Children's Clinic · USNew Jersey Institute of Technology · USPennsylvania State University · USPrimary Children's Hospital · USRoyal Children's Hospital · AU
Funding
LCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., KISSELA, BRETT M · 2015 to 2024
$37.5MRegulation of IgA class switching in the intestinal mucosaP01AI061093 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI CASANOVA, JEAN-LAURENT · 2004 to 2021
$29.8MVITAMIN K DEFICIENCY IN CHOLESTATIC LIVER DISEASEM01RR008084 · NCRR · CINCINNATI CHILDRENS HOSP MED CTR · PI STRAUSS, ARNOLD W · 1994 to 2009
$20.6MROLE OF ANGPTL4, AN ANGIOGENIC MEDIATOR, IN ARTHRITISP30AR047363 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI WAGNER, MICHAEL · 2001 to 2015
$9.2MResources to Assist Investigations in Primary Immunodeficiency Diseases (U24)U24AI086037 · NIAID · IMMUNE DEFICIENCY FOUNDATION · PI CUNNINGHAM-RUNDLES, CHARLOTTE · 2010 to 2019
$6.5MTARGETING PRIMARY IMMUNODEFICIENCY AMONG MINORITIESR18AI048693 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI CUNNINGHAM-RUNDLES, CHARLOTTE · 2000 to 2016
$6.2MFine Mapping and Functional Evaluation of Selected Type 1 Diabetes LociDP3DK085708 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI HAKONARSON, HAKON, POLYCHRONAKOS, CONSTANTIN · 2009 to 2009
$4.8MIntegrative Analysis of a GWAS Repository with EMRs from over 40,000 ChildrenU01HG006830 · NHGRI · CHILDREN'S HOSP OF PHILADELPHIA · PI HAKONARSON, HAKON · 2012 to 2014
$3.7MMethods for genomic data with graphical structuresR01CA127334 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LEE, HONGZHE · 2007 to 2016
$2.6MThe X-factor of complex disease: From population genetics to GWAS of Chromosome XR01HG006849 · NHGRI · CORNELL UNIVERSITY · PI CLARK, ANDREW G · 2013 to 2020
$2.3MDefining the complex genetics of JIARC1AR058587 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI THOMPSON, SUSAN D · 2009 to 2010
$1.0MGenetics of Juvenile Idiopathic ArthritisRC1AR058606 · NIAMS · CHILDREN'S HOSP OF PHILADELPHIA · PI FINKEL, TERRI H, HAKONARSON, HAKON · 2009 to 2010
$999kChief Scientist Office ETM/137Chief Scientist Office ETM/75Howard Hughes Medical InstituteMedical Research Council G0600329Medical Research Council G0800675Medical Research Council G0800759MRF_ C0482NCATS NIH HHS UL1 TR001425NCI NIH HHS CA127334NCI NIH HHS R01 CA127334NHGRI NIH HHS R01 HG006849NHGRI NIH HHS R01-HG006849NHGRI NIH HHS U01 HG006830NHGRI NIH HHS U01HG006830NIAMS NIH HHS F30 AR066486NIAMS NIH HHS RC1 AR058587NIAMS NIH HHS RC1 AR058606NIAMS NIH HHS RC1AR058606NIDDK NIH HHS DP3 DK085708NIDDK NIH HHS DP3DK085708Wellcome TrustWellcome Trust 076113
Abstract
Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases.
Indexed as
Autoimmune DiseasesChildGenome-Wide Association StudyHumansPolymorphism, Single NucleotideQuantitative Trait LociRisk Factors
Identifiers
What Socratic holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.