ArticleAnnals of the rheumatic diseases2025
Genome-wide association study in chondrocalcinosis reveals ENPP1 as a candidate therapeutic target in calcium pyrophosphate deposition disease.
Article in Annals of the rheumatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Follow the Molecule from Crystal Arthropathy to Comorbidities: The 2024 G-CAN Gold Medal Award Awardee Lecture.Gout, urate, and crystal deposition disease · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
objectivesThe genetic basis of calcium pyrophosphate deposition (CPPD) disease is unknown. This limits the development of therapeutic strategies. We aimed to analyse a genome-wide association study (GWAS) on a large administrative database to identify new candidate causal genes for CPPD disease.
methodsWe used publicly available GWAS summary statistics for Phecode-defined chondrocalcinosis and crystal arthropathy from the Veterans Affairs Million Veteran Program in people of African (AFR) and European (EUR) ancestry. Included were 3004 (536 AFR and 2468 EUR) cases for chondrocalcinosis and 3766 (700 AFR and 3066 EUR) cases for crystal arthropathy (operationally interpreted as calcium crystal arthropathy). Our primary analysis was in chondrocalcinosis, with secondary analysis in crystal arthropathy. We tested for colocalisation of chondrocalcinosis genetic association signals with genetic control of gene expression.
resultsThere were 2 genome-wide significant loci for chondrocalcinosis in both AFR and EUR cases, both on chromosome 6 (signals within the ENPP1 and RNF144B genes). Findings were supported by analysis of the crystal arthropathy cohort. Colocalisation analysis of chondrocalcinosis genetic association signals with genetic control of gene expression and alternative splicing further supported ENPP1 and RNF144B as candidate casual genes. At ENPP1, the allele that increases the risk for chondrocalcinosis was associated with increased ENPP1 expression.
conclusionsENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (NPP1) that produces adenosine monophosphate (AMP) and inorganic pyrophosphate which, together with calcium ions, leads to the formation of calcium pyrophosphate crystals. Selective NPP1 inhibitors developed for infectious disease and cancer could be tested as treatment for CPPD disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.