.png){kind=icon}
.png){kind=icon}
Return
Cross-trait genetic analysis maps shared polygenic architecture between primary aldosteronism and blood pressure to adrenal cell states
.png){kind=icon}
OA
AI
Z
C
Y
N
T
DOI：10.1186/s12967-026-08819-2.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Primary aldosteronism (PA) is a major cause of endocrine hypertension and contributes substantially to blood pressure (BP)-related morbidity. Although aldosterone excess directly raises BP, the extent to which genetic susceptibility to PA overlaps with the broader polygenic architecture of BP remains unclear. We aimed to characterise the shared genetic architecture between PA and BP traits and to place shared genetic signals within adrenal tissue context. We analysed genetic overlap between PA and BP using two independent PA datasets from the French COMETE Network and the US Million Veteran Program, together with genome-wide association data for systolic BP, diastolic BP and pulse pressure. Analyses included genome-wide and regional genetic correlation, cross-trait meta-analysis to identify shared genetic signals and complementary gene-prioritisation approaches. Biological context was assessed using functional annotation, tissue-specific expression analyses and integration with single-cell and spatial transcriptomic datasets from human adrenal tissue. PA showed significant positive genetic correlations with all three BP traits, with six genomic regions showing evidence of shared regional association. Cross-trait meta-analysis and co-localisation identified 143 independent shared signals associated with both PA and BP, with variant annotations indicating regulatory activity across adrenal, vascular, cardiac, adipose and neuroendocrine tissues. Gene-based analyses prioritised 43 candidate genes supported by convergent analytical approaches and implicated pathways related to vascular remodelling, extracellular matrix organisation, ion transport and endocrine regulation. Integration with adrenal single-cell and spatial transcriptomic data demonstrated that prioritised genes are expressed within defined adrenal cellular compartments, including aldosterone-producing populations. Among these candidates, SLC24A3 showed enriched expression in aldosterone-producing adenoma cells, with spatially heterogeneous expression associated with steroidogenic versus stress-adaptive transcriptional programmes. These findings support adrenal cell-state specificity of shared genetic signals and argue against a purely generic background BP-genetic explanation, without establishing causality for individual genes. PA and BP share a polygenic architecture that maps to adrenal endocrine cell states and vascular regulatory programmes within the intrinsic adrenal microenvironment. These findings link inherited BP-related variation to adrenal tissue biology and identify shared genetic signals, prioritised genes and cell states that may inform future studies of PA risk stratification, endocrine hypertension screening and cardiovascular risk prevention.
Keywords:
Adrenal cortex
Blood pressure
Cross-trait genetic analysis
Endocrine hypertension
Polygenic architecture
Primary aldosteronism
Single-cell transcriptomics
Spatial transcriptomics
Journal
IF:
7.5
Papers:
9.3K
Citations:
3.2W
Organization
Cited Papers