ArticlePloS one2014
Integration of sequence data from a Consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene.
Open access · goldAbstract read
In one paragraph
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
8.1field-weighted citation impact, top 2% 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
18 citing papers in PubMed, 149 citations in OpenAlex.
- Epidemiology and Genetics of Rheumatic Diseases Suggest a Constant Rate of DNA Damage as Underlying Cause.Immunology · 2026Article
- Low-frequency and rare genetic variants associated with rheumatoid arthritis risk.Nature reviews. Rheumatology · 2024Review
- Multi-omics profiling reveals potential alterations in rheumatoid arthritis with different disease activity levels.Arthritis research & therapy · 2023Article
- Multidimensional analyses of the pathomechanism caused by the non-catalytic GNE variant, c.620A>T, in patients with GNE myopathy.Scientific reports · 2022Article
- Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease.Gastroenterology report · 2021Article
- Post-GWAS functional studies reveal an RA-associated CD40-induced NF-kB signal transduction and transcriptional regulation network targeted by class II HDAC inhibitors.Human molecular genetics · 2021Article
- Obelisc: an identical-by-descent mapping tool based on SNP streak.Bioinformatics (Oxford, England) · 2021Article
- Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy.Frontiers in immunology · 2021Article
- Review
- Article
- A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation.Immunity · 2018Article
- Genome-Wide Identification of NFrontiers in genetics · 2018Article
- Family studies to find rare high risk variants in migraine.The journal of headache and pain · 2017Review
- Update on the genetic architecture of rheumatoid arthritis.Nature reviews. Rheumatology · 2017Review
- Applications of Next-generation Sequencing in Systemic Autoimmune Diseases.Genomics, proteomics & bioinformatics · 2015Review
- Genetic architectures of seropositive and seronegative rheumatic diseases.Nature reviews. Rheumatology · 2015Review
- The axis of progression of disease.Cancer informatics · 2014Article
- Use of next-generation DNA sequencing to analyze genetic variants in rheumatic disease.Arthritis research & therapy · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
48 authors at 20 institutions in 10 countries.
Yukinori OkadaDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America ; Department of Human Genetics and Disease Diversity, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan ; Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Dorothee DiogoDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
Jeffrey D GreenbergNew York University Hospital for Joint Diseases, New York, New York, United States of America.
Faten MouassessMolecular Biology and Biotechnology Department, Human Genetics Division, Damascus, Syria.
Walid A L AchkarMolecular Biology and Biotechnology Department, Human Genetics Division, Damascus, Syria.
Robert S FultonThe Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Joshua C DennyDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Namrata GuptaProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
Daniel MirelProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
Stacy GabrielProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
Gang LiDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Joel M KremerDepartment of Medicine, Albany Medical Center and The Center for Rheumatology, Albany, New York, United States of America.
Dimitrios A PappasDivision of Rheumatology, Department of Medicine, New York, Presbyterian Hospital, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
Robert J CarrollDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Anne E EylerDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Gosia TrynkaDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
Eli A StahlThe Department of Psychiatry at Mount Sinai School of Medicine, New York, New York, United States of America.
Jing CuiDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Richa SaxenaCenter for Human Genetics Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Marieke J H CoenenDepartment of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
Henk-Jan GuchelaarDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Tom W J HuizingaDepartment of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Philippe DieudéService de Rhumatologie et INSERM U699 Hôpital Bichat Claude Bernard, Assistance Publique des Hôpitaux de Paris, Paris, France ; Université Paris 7-Diderot, Paris, France.
Xavier MarietteInstitut National de la Santé et de la Recherche Médicale (INSERM) U1012, Université Paris-Sud, Rhumatologie, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France.
Anne BartonArthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Helena CanhãoRheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal ; Rheumatology Department, Santa Maria Hospital-CHLN, Lisbon, Portugal.
João E FonsecaRheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal ; Rheumatology Department, Santa Maria Hospital-CHLN, Lisbon, Portugal.
Niek de VriesDepartment of Clinical Immunology and Rheumatology & Department of Genome Analysis, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Paul P TakDepartment of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands ; GlaxoSmithKline, Stevenage, United Kingdom.
Larry W MorelandDivision of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
S Louis BridgesDivision of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Corinne Miceli-RichardInstitut National de la Santé et de la Recherche Médicale (INSERM) U1012, Université Paris-Sud, Rhumatologie, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France.
Hyon K ChoiChanning Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Section of Rheumatology, Boston University School of Medicine, Boston, Massachusetts, United States of America ; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Yoichiro KamataniLaboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan ; Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France.
Pilar GalanUniversité Paris 13 Sorbonne Paris Cité, UREN (Nutritional Epidemiology Research Unit), Inserm (U557), Inra (U1125), Cnam, Bobigny, France.
Mark LathropMcGill University and Génome Québec Innovation Centre, Montréal, Canada.
Towfique RajDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America ; Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Philip L De JagerDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America ; Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Soumya RaychaudhuriDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America ; NIHR Manchester Musculoskeletal Biomedical, Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
Jane WorthingtonArthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom ; National Institute for Health Research, Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals National Health Service Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
Leonid PadyukovRheumatology Unit, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
Lars KlareskogRheumatology Unit, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
Katherine A SiminovitchLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada ; Toronto General Research Institute, Toronto, Canada ; Department of Medicine, University of Toronto, Toronto, Canada.
Peter K GregersenThe Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, United States of America.
Elaine R MardisThe Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Thurayya ArayssiWeill Cornell Medical College-Qatar, Education City, Doha, Qatar.
Layla A KazkazTishreen Hospital, Damascus, Syria ; Syrian Association for Rheumatology, Damascus, Syria.
Robert M PlengeDivision of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
Broad Institute · USBrigham and Women's Hospital · USVanderbilt University · USAmsterdam UMC Location University of Amsterdam · NLHarvard University · USInserm · FRKarolinska Institutet · SELeiden University Medical Center · NLManchester Academic Health Science Centre · GBWashington University in St. Louis · USAlbany Medical Center Hospital · USAssistance Publique – Hôpitaux de Paris · FRColumbia University · USFondation Jean Dausset-CEPH · FRHospital de Santa Maria · PTIcahn School of Medicine at Mount Sinai · USLatakia University · SYLunenfeld-Tanenbaum Research Institute · CAMassachusetts General Hospital · USMcGill University and Génome Québec Innovation Centre · CA
Funding
WORK DISABILITY-- PERSONS WITH RHEUMATOID ARTHRITISP60AR047785 · NIAMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ZHANG, YUQING · 2001 to 2016
$18.0MGenetic predictors of response to anti-TNF therapy in rheumatoid arthritisU01GM092691 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2010 to 2014
$7.5MDiscovery and Functional Impact of Common and Rare Variants in RAR01AR063759 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2013 to 2026
$5.4MNOVEL METABOLITE AND MICROBIOTA PATHWAYS FOR HYPERURICEMIA AND GOUTR01AR065944 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI CHOI, HYON K · 2013 to 2025
$4.2MGenetics of GoutR01AR056291 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI CHOI, HYON K · 2008 to 2011
$2.9MNEXT GENERATION SEQUENCING ADD-ON-PHARMACOGENOMICS RESEARCH NETWROK (PGRN)U01GM097119 · NIGMS · WASHINGTON UNIVERSITY · PI MARDIS, ELAINE R · 2010 to 2014
$2.6MDissection of two rheumatoid arthritis risk loci from genome-wide studiesR01AR056768 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B. · 2009 to 2013
$1.9MBioinformatics and Population Genetics to Identify Rheumatoid Arthritis GenesK08AR055688 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI RAYCHAUDHURI, SOUMYA · 2008 to 2012
$724kMeta-analysis of GWAS data to identify novel rheumatoid arthritis risk lociR01AR057108 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI PLENGE, ROBERT M · 2009 to 2010
$557kDeep Re-Sequencing of Rheumatoid Arthritis Risk LociR01AR059648 · NIAMS · BROAD INSTITUTE, INC. · PI PLENGE, ROBERT M · 2010 to 2011
$493kRisk Factors for Gout Among WomenR21AR056042 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI CHOI, HYON K · 2008 to 2009
$424kArthritis Research UK 20385CIHR MOP79321Department of Health MANMKBRU-2012-1NIAMS NIH HHS K08 AR055688NIAMS NIH HHS P60 AR047785NIAMS NIH HHS R01 AR056291NIAMS NIH HHS R01-AR056291NIAMS NIH HHS R01 AR056768NIAMS NIH HHS R01-AR056768NIAMS NIH HHS R01 AR057108NIAMS NIH HHS R01-AR057108NIAMS NIH HHS R01 AR059648NIAMS NIH HHS R01-AR059648NIAMS NIH HHS R01 AR063759NIAMS NIH HHS R01AR063759-01A1NIAMS NIH HHS R01 AR065944NIAMS NIH HHS R01-AR065944NIAMS NIH HHS R21 AR056042NIGMS NIH HHS U01 GM092691NIGMS NIH HHS U01-GM092691NIGMS NIH HHS U01 GM097119PHS HHS K08-KAR055688A
Abstract
Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2 × 10(-6)). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted.
Indexed as
ConsanguinityGenetic Predisposition to DiseaseGenome-Wide Association StudyArthritis, RheumatoidBase SequenceCohort StudiesExomeExonsFemaleGenetic LociGenotyping TechniquesHigh-Throughput Nucleotide SequencingHumansLysophospholipaseMaleMeta-Analysis as TopicLysophospholipase
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
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 OpenQuestion graph.