Evidence map›Paper›PMID 37461309›Full record

SynthesiseLife2023

Genetic insights into ossification of the posterior longitudinal ligament of the spine.

Yoshinao Koike, Masahiko Takahata, Masahiro Nakajima, Nao Otomo, Hiroyuki Suetsugu, Xiaoxi Liu, Tsutomu Endo, Shiro Imagama, Kazuyoshi Kobayashi, Takashi Kaito and 42 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
10.3field-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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. How gut microbiome and blood metabolites drive ossification of the posterior longitudinal ligament of the spine: a genome-wide association study based on the East Asian population.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 · 2026
    Article
  4. Integrative Transcriptomic Profiling Delineates LTBP4-Driven Fibroblast Reprogramming Across the Ossification Continuum of the Ligamentum Flavum.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  5. Review
  6. Whole-spine CT predictors of lumbar surgery in patients with ossification of the posterior longitudinal ligament.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 · 2026
    Article
  7. Article
  8. [Radiological characteristics and associated factors of single-level cervical disc herniation combining with focal ossification of posterior longitudinal ligament].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Identification of Risk Factors for Primary Osteoporosis: The Role of Cervical Ligament Ossification.Medical science monitor : international medical journal of experimental and clinical research · 2024
    Article
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

52 authors at 20 institutions in 2 countries.

Yoshinao Koike *Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.ORCID 0000-0002-5431-5572
Masahiko Takahata *Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Masahiro Nakajima *Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
Nao OtomoLaboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
Hiroyuki SuetsuguLaboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
Xiaoxi LiuLaboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Tsutomu EndoDepartment of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Shiro ImagamaDepartment of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kazuyoshi KobayashiDepartment of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takashi KaitoDepartment of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Satoshi KatoDepartment of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Yoshiharu KawaguchiDepartment of Orthopaedic Surgery, Toyama University, Toyama, Japan.
Masahiro KanayamaDepartment of Orthopedics, Hakodate Central General Hospital, Hakodate, Japan.
Hiroaki SakaiDepartment of Orthopaedic Surgery, Spinal Injuries Center, Iizuka, Japan.
Takashi TsujiDepartment of Orthopedic Surgery, Keio University School of Medicine, Nagoya, Japan.
Takeshi MiyamotoDepartment of Orthopedic Surgery, Keio University School of Medicine, Nagoya, Japan.
Hiroyuki InoseDepartment of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.ORCID 0000-0003-4195-2545
Toshitaka YoshiiDepartment of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Masafumi KashiiDepartment of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Hiroaki NakashimaDepartment of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kei AndoDepartment of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yuki TaniguchiDepartment of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.ORCID 0000-0002-2329-123X
Kazuhiro TakeuchiDepartment of Orthopaedic Surgery, National Okayama Medical Center, Okayama, Japan.
Shuji ItoLaboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Kohei TomizukaLaboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Keiko HikinoLaboratory for Pharmacogenomics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Yusuke IwasakiLaboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Yoichiro KamataniLaboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Shingo MaedaDepartment of Bone and Joint Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Hideaki NakajimaDepartment of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Kanji MoriDepartment of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Japan.
Atsushi SeichiDepartment of Orthopedics, Jichi Medical University, Shimotsuke, Japan.
Shunsuke FujibayashiDepartment of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tsukasa KanchikuDepartment of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Kei WatanabeDepartment of Orthopaedic Surgery, Niigata University Medical and Dental General Hospital, Nankoku, Japan.
Toshihiro TanakaDepartment of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Kazunobu KidaDepartment of Orthopaedic Surgery, Kochi Medical School, Nankoku, Japan.
Sho KobayashiDepartment of Orthopaedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.ORCID 0000-0002-8002-2001
Masahito TakahashiDepartment of Orthopaedic Surgery, Kyorin University School of Medicine, Tokyo, Japan.
Kei YamadaDepartment of Orthopaedic Surgery, Kurume University School of Medicine, Obu, Japan.
Hiroshi TakuwaLaboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
Hsing-Fang LuLaboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
Shumpei NiidaCore Facility Administration, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.ORCID 0000-0002-6192-8035
Kouichi OzakiMedical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, Obu, Japan.
Yukihide MomozawaLaboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Genetic Study Group of Investigation Committee on Ossification of the Spinal Ligaments
Masashi YamazakiDepartment of Orthopaedic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Atsushi OkawaDepartment of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Morio MatsumotoDepartment of Orthopedic Surgery, Keio University School of Medicine, Nagoya, Japan.
Norimasa IwasakiDepartment of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Chikashi TeraoLaboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.ORCID 0000-0002-6452-4095
Shiro IkegawaLaboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
RIKEN Center for Integrative Medical Sciences · JPHokkaido University · JPNagoya University · JPKeio University · JPTokyo Medical and Dental University · JPNational Center for Geriatrics and Gerontology · JPShimane University · JPThe University of Osaka · JPFujita Health University · JPHakodate Central General Hospital · JPHamamatsu University School of Medicine · JPHirosaki University · JPJichi Medical University · JPKagoshima University · JPKanazawa University · JPKochi Medical School Hospital · JPKurume University · JPKyorin University · JPKyoto University · JPKyushu University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.

Indexed as

Diabetes Mellitus, Type 2Ossification of Posterior Longitudinal LigamentAnimalsGenome-Wide Association StudyMiceOsteogenesisSpinebone mineral densitygeneticsgenome-wide association studygenomicshumanMendelian randomizationobesityossification of the posterior longitudinal ligament of the spinepolygenic risk score

Identifiers

PMID37461309
PMCPMC10353864
OpenAlexW4384627333

What Socratic 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 Socratic graph.