ArticleHuman molecular genetics2026
Multi-omics investigation of thyroid development and dysfunction in down syndrome.
Article in Human molecular genetics, 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
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDown syndrome (DS), caused by trisomy of chromosome 21, is associated with a high prevalence of congenital non-autoimmune thyroid dysfunction, typically characterized by an elevated serum thyroid stimulating hormone (TSH) concentration. Early-life observational studies and fetal cordocentesis data, consistently reporting elevated TSH levels, suggest a developmental origin. However, the underlying pathophysiological mechanism remains unclear. This study aimed to investigate the molecular and developmental features underlying thyroid dysfunction in DS.
methodsThyroid tissue of fetuses with DS (n = 4) and fetuses without a genetic/developmental abnormality (n = 5) were analyzed using histology, bulk RNA sequencing (RNA-seq), and DNA methylation (DNAm) profiling.
resultsHistological analysis revealed underdevelopment of DS fetal thyroid tissue, with smaller follicles and greater heterogeneity. RNA-seq identified 1035 differentially expressed genes (DEGs) distributed across the genome. Notably, three thyroid-relevant genes, FOXE1, IYD, and DIO2, were significantly downregulated in DS tissue. Gene set enrichment analysis (GSEA) showed widespread disruption of cellular processes. DNAm analysis identified 266 differentially methylated regions (DMRs), several of which overlapped with loci previously implicated in DS. Integration of expression and DNAm data revealed 20 significant integrative methylation-expression analysis associations, indicating cis-regulatory DNAm effects on gene expression.
conclusionsThese findings suggest that congenital thyroid dysfunction in DS represents a DS-specific form of thyroid dysfunction, characterized by impaired thyroid development and altered expression and regulation of genes involved in thyroid function and general cellular processes. The genome-wide molecular changes observed likely result from gene dosage effects and systemic (epi)genomic disturbances caused by trisomy 21.
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.