Evidence map›Paper›PMID 30261039›Full record

SynthesisPLoS genetics2018

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain.

Pradeep Suri, Melody R Palmer, Yakov A Tsepilov, Maxim B Freidin, Cindy G Boer, Michelle S Yau, Daniel S Evans, Andrea Gelemanovic, Traci M Bartz, Maria Nethander and 27 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 9 pooled it
13.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 9 syntheses or guidelines pooled it, 163 citations in OpenAlex.

  1. Pooled it
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  7. Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2022
    Pooled it
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  9. ISSLS Prize in Clinical Science 2020. Examining causal effects of body mass index on back pain: a Mendelian randomization study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020 · on this map
    Pooled it
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  19. Challenges and opportunities for omics-based precision medicine in chronic low back pain.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025
    Review
  20. Mechanism-based nonopioid analgesic targets.The Journal of clinical investigation · 2025
    Review

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

37 authors at 20 institutions in 6 countries.

Pradeep SuriSeattle Epidemiologic Research and Information Center (ERIC), Department of Veterans Affairs Office of Research and Development, Seattle, Washington, United States of America.ORCID 0000-0002-9449-4165
Melody R PalmerMedical Genetics, Department of Medicine, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0003-4252-4518
Yakov A TsepilovPolyomica, 's-Hertogenbosch, the Netherlands.ORCID 0000-0002-4931-6052
Maxim B FreidinDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.ORCID 0000-0002-1439-6259
Cindy G BoerDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.ORCID 0000-0003-4809-0044
Michelle S YauInstitute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, United States of America.
Daniel S EvansCalifornia Pacific Medical Center Research Institute, San Francisco, California, United States of America.
Andrea GelemanovicDepartment of Public Health, University of Split Medical School, Split, Croatia.ORCID 0000-0001-9195-646X
Traci M BartzCardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0003-3403-8763
Maria NethanderDepartment of Medicine, University of Göteborg, Göteborg, Sweden.ORCID 0000-0003-3688-906X
Liubov ArbeevaDepartment of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Lennart KarssenPolyomica, 's-Hertogenbosch, the Netherlands.ORCID 0000-0002-1959-342X
Tuhina NeogiClinical Epidemiology Unit, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Archie CampbellCentre for Genomic and Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0003-0198-5078
Dan MellstromGeriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Sweden.
Claes OhlssonDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Göteborg, Sweden.
Lynn M MarshallDepartment of Orthopedics and Rehabilitation, Oregon Health and Science University, Portland, Oregon, United States of America.ORCID 0000-0002-2500-8784
Eric OrwollDepartment of Medicine, Oregon Health and Science University, Portland, Oregon, United States of America.
Andre UitterlindenDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, United States of America.ORCID 0000-0001-7191-1723
Gordan LaucGenos Ltd, Osijek, Croatia.ORCID 0000-0003-1840-9560
Bruce M PsatyCardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington, United States of America.
Magnus K KarlssonDepartment of Orthopedics, Skane University Hospital, Lund University, Malmö, Sweden.
Nancy E LaneDepartments of Medicine and Rheumatology, University of California Davis, Sacramento, California, United States of America.
Gail P JarvikMedical Genetics, Department of Medicine, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0002-6710-8708
Ozren PolasekDepartment of Public Health, University of Split Medical School, Split, Croatia.
Marc HochbergDepartments of Medicine and Epidemiology, University of Maryland, Baltimore, Maryland, United States of America.
Joanne M JordanDepartment of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Joyce B J Van MeursDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Rebecca JacksonDepartment of Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Carrie M NielsonSchool of Public Health, Oregon Health and Science University, Portland, Oregon, United States of America.
Braxton D MitchellDepartments of Medicine and Epidemiology, University of Maryland, Baltimore, Maryland, United States of America.
Blair H SmithDivision of Population Health Sciences, School of Medicine, University of Dundee, Dundee, United Kingdom.ORCID 0000-0002-5362-9430
Caroline HaywardMRC Human Genetics Unit, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, United Kingdom.
Nicholas L SmithSeattle Epidemiologic Research and Information Center (ERIC), Department of Veterans Affairs Office of Research and Development, Seattle, Washington, United States of America.
Yurii S AulchenkoPolyomica, 's-Hertogenbosch, the Netherlands.ORCID 0000-0002-7899-1575
Frances M K WilliamsDepartment of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.ORCID 0000-0002-2998-2744
Erasmus MC · NLOregon Health & Science University · USUniversity of Gothenburg · SEUniversity of Washington · USExpertise Center Vocational Education · NLInstitute of Genetics and Cancer · GBKaiser Permanente Washington Health Research Institute · USKing's College London · GBUniversity of Maryland, Baltimore · USUniversity of North Carolina at Chapel Hill · USBeth Israel Deaconess Medical Center · USBoston University · USCalifornia Pacific Medical Center · USLund University · SENovosibirsk State University · RUPsychiatric Hospital Sveti Ivan · HRThe Lundquist Institute · USThe Ohio State University · USUniversity of California, Davis · USUniversity of Dundee · GB

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
OREGON CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024140 · NCRR · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2006 to 2011
$61.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7M
Study of Osteoporotic FracturesR01AG005407 · NIA · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI CUMMINGS, STEVEN RON, YAFFE, KRISTINE · 1986 to 2016
$23.2M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
WORK DISABILITY-- PERSONS WITH RHEUMATOID ARTHRITISP60AR047785 · NIAMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI NEOGI, TUHINA · 2001 to 2016
$18.0M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
EPIDEMIOLOGY OF DEMENTIA IN THE FRAMINGHAM STUDYR01AG008122 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA, SESHADRI, SUDHA · 1989 to 2015
$14.4M
OSTEOPOROTIC FRACTURES IN MENU01AG018197 · NIA · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI CUMMINGS, STEVEN RON · 1999 to 2011
$12.7M
MRI, Genetics &Cognitive Precursors of AD &DementiaR01AG016495 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA · 1999 to 2016
$12.5M
ARRA NIH HHSMedical Research Council MC_PC_17228Medical Research Council MC_PC_U127561128Medical Research Council MC_QA137853Medical Research Council MC_UU_00007/10NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR000128NCATS NIH HHS UL1 TR002369NCCDPHP CDC HHS U01 DP006266NCRR NIH HHS UL1 RR024140NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL130114NIAMS NIH HHS K24 AR070892NIAMS NIH HHS P60 AR030701NIAMS NIH HHS P60 AR047785NIAMS NIH HHS P60 AR049465NIAMS NIH HHS R01 AR035582NIAMS NIH HHS R01 AR035583NIAMS NIH HHS R01 AR035584NIAMS NIH HHS R01 AR062506NIAMS NIH HHS RC2 AR058950NIAMS NIH HHS RC2 AR058973NIAMS NIH HHS U01 AR045580NIAMS NIH HHS U01 AR045583NIAMS NIH HHS U01 AR045614NIAMS NIH HHS U01 AR045632NIAMS NIH HHS U01 AR045647NIAMS NIH HHS U01 AR045654NIAMS NIH HHS U01 AR066160NIA NIH HHS R01 AG005394NIA NIH HHS R01 AG005407NIA NIH HHS R01 AG008122NIA NIH HHS R01 AG016495NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG027574NIA NIH HHS R01 AG027576NIA NIH HHS U01 AG018197NIA NIH HHS U01 AG027810NIA NIH HHS U01 AG042124NIA NIH HHS U01 AG042139NIA NIH HHS U01 AG042140NIA NIH HHS U01 AG042143NIA NIH HHS U01 AG042145NIA NIH HHS U01 AG042168NIA NIH HHS U24 AG051129NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK072488NINDS NIH HHS R01 NS017950RRD VA IK2 RX001515Wellcome TrustWellcome Trust 104036/Z/14/ZWHI NIH HHS HHSN268200900009C
6 · The paper itself

Abstract

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. CBP cases were defined as those reporting back pain present for ≥3-6 months; non-cases were included as comparisons ("controls"). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5×10(-8). Suggestive (p<5×10(-7)) and genome-wide significant (p<5×10(-8)) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p = 7.2×10(-10)). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10(-11)), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10(-19)). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p = 4.4×10(-13)), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10(-10)). In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).

Indexed as

Genetic LociBack PainBiomarkers, TumorChronic PainDCC ReceptorDNA-Binding ProteinsGasderminsGenome-Wide Association StudyHumansIntracellular Signaling Peptides and ProteinsIntronsPolymorphism, Single NucleotideRNA, Long NoncodingSOXD Transcription FactorsWhite PeopleBiomarkers, TumorDCC protein, humanDCC ReceptorDNA-Binding ProteinsGasderminsGSDMC protein, humanIntracellular Signaling Peptides and Proteinslong noncoding RNA CCDC26, humanRNA, Long NoncodingSOX5 protein, humanSOXD Transcription Factors

Identifiers

PMID30261039
PMCPMC6159857
OpenAlexW2953297691

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.