ArticleScientific reports2026
Integrated multi-omics analysis combined with clinical validation reveals that HLA-DRB5 and ODAPH are causal risk genes for keratoconus.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aimed to elucidate the genetic determinants of keratoconus (KC) using a multi-omics approach, with a focus on identifying key causal genes to address gaps in understanding the disease’s pathological mechanisms. An integrated multi-omics study combining bioinformatics analysis of transcriptome data with clinical validation. This approach does not include a traditional control group but utilizes public databases and patient samples to assess genetic associations. Five KC patients from the First Affiliated Hospital of Xi’an Jiaotong University provided corneal tissues and blood samples. The control group consisted of five age-matched donors who provided excess corneal tissue from transplantation surgeries. The study involved analyzing two KC transcriptome datasets from GEO to identify differentially expressed genes (DEGs). This was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, summary-data Mendelian randomization (SMR), two-sample Mendelian randomization (TSMR), Bayesian colocalization, and clinical validation through immunohistochemical staining and PCR assays. Primary measures included gene expression levels, causal association statistics (e.g., posterior probability PP4, SMR p-value, OR), and RNA and protein expression of key genes (HLA-DRB5, ODAPH, MMP-9) assessed through molecular assays. The analysis identified 2,884 DEGs enriched in cell adhesion, immune response, and the TNF and IL-17 signaling pathways. Twenty-four genes demonstrated strong causal associations with KC (PP4 > 0.8), with HLA-DRB5 (PP4 = 0.844, SMR p = 0.001, OR = 1.768) and ODAPH (PP4 = 1.0, SMR p = 0.013, OR = 202.851) showing the highest confidence. Clinical validation confirmed significantly elevated expression of HLA-DRB5, ODAPH, and MMP-9 in the KC cornea and whole blood. HLA-DRB5 and ODAPH were identified as key causal risk genes for KC, bridging critical gaps in genetic knowledge and providing a foundation for early diagnostic biomarkers and etiology-targeted therapies, such as Meplazumab, an HLA-DRB5 inhibitor.
Indexed as
Identifiers
What Socratic 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 Socratic graph.