ArticleHuman molecular genetics2016
A polygenic burden of rare variants across extracellular matrix genes among individuals with adolescent idiopathic scoliosis.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci.Human molecular genetics · 2018Pooled it
- Massively parallel characterization of adolescent idiopathic scoliosis risk variants.Genome research · 2026Article
- Preoperative mid-cervical disc degeneration is associated with residual cervical kyphosis after surgery for adolescent idiopathic scoliosis.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 · 2026Article
- Deletion of aJOR spine · 2026Article
- FLNB and TTC26 regulate ciliary Hedgehog signaling to maintain intervertebral disc matrix homeostasis in adolescent idiopathic scoliosis.Genome biology · 2026Article
- Genetic interaction betweenResearch square · 2026Article
- Genetic interaction betweenbioRxiv : the preprint server for biology · 2026Article
- Association of Sleep Patterns with the Development of Idiopathic Scoliosis: A Nationwide Pediatric Cohort Study.Clinics in orthopedic surgery · 2026Observational
- The role of genetics and molecular mechanisms in early onset scoliosis.Journal of clinical orthopaedics and trauma · 2026Review
- Oxidative stress-induced intervertebral disc remodelling and elevated stiffness drive idiopathic scoliosis in preclinical models.Nature communications · 2025Article
- The importance of imperfect pre-clinical models in adolescent idiopathic scoliosis.Disease models & mechanisms · 2025Review
- EPHA4 signaling dysregulation links abnormal locomotion and the development of idiopathic scoliosis.eLife · 2025Article
- Rare missense variants inJournal of medical genetics · 2025Article
- Plasma exosome proteomics reveals upregulation of CILP-1 in concave side of paraspinal muscle in adolescent idiopathic scoliosis.Clinical proteomics · 2025Article
- Gut microbiota alterations in adolescent idiopathic scoliosis: a comparison study with healthy control and congenital scoliosis.Spine deformity · 2025Article
- Genetics and pathogenesis of scoliosis.North American Spine Society journal · 2024Article
- Rare variant association analyses reveal the significant contribution of carbohydrate metabolic disturbance in severe adolescent idiopathic scoliosis.Journal of medical genetics · 2024Article
- Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis.Orthopaedic surgery · 2024Article
- Association of genetic variation ineLife · 2024Article
- Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Adolescent idiopathic scoliosis (AIS) is a complex inherited spinal deformity whose etiology has been elusive. While common genetic variants are associated with AIS, they explain only a small portion of disease risk. To explore the role of rare variants in AIS susceptibility, exome sequence data of 391 severe AIS cases and 843 controls of European ancestry were analyzed using a pathway burden analysis in which variants are first collapsed at the gene level then by Gene Ontology terms. Novel non-synonymous/splice-site variants in extracellular matrix genes were significantly enriched in AIS cases compared with controls (P = 6 × 10(-9), OR = 1.7, CI = 1.4-2.0). Specifically, novel variants in musculoskeletal collagen genes were present in 32% (126/391) of AIS cases compared with 17% (146/843) of in-house controls and 18% (780/4300) of EVS controls (P = 1 × 10(-9), OR = 1.9, CI = 1.6-2.4). Targeted resequencing of six collagen genes replicated this association in combined 919 AIS cases (P = 3 × 10(-12), OR = 2.2, CI = 1.8-2.7) and revealed a highly significant single-gene association with COL11A2 (P = 6 × 10(-9), OR = 3.8, CI = 2.6-7.2). Importantly, AIS cases harbor mainly non-glycine missense mutations and lack the clinical features of monogenic musculoskeletal collagenopathies. Overall, our study reveals a complex genetic architecture of AIS in which a polygenic burden of rare variants across extracellular matrix genes contributes strongly to risk.
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