| Title: | Genetic Architecture of N-Terminal Pro-B-Type Natriuretic Peptide in a Multiancestry Study Population |
| Journal: | Circulation Genomic and Precision Medicine |
| Published: | 28 Jan 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41603044/ |
| DOI: | https://doi.org/10.1161/circgen.124.005130 |
Publication 18450
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population.</p>
METHODS: Whole genome sequencing and array-based data from 81 213 individuals without heart failure were analyzed from the Trans-Omics for Precision Medicine cohorts, UK Biobank, All of Us Research Program, and REGARDS (Reasons for Geographic and Racial Differences in Stroke) study to identify common, rare, and structural variants associated with NT-proBNP levels. The main outcome of the study was rank-based inverse normal and standardized NT-proBNP levels. Genetic associations with NT-proBNP were examined, followed by gene prioritization, transcriptome-wide association studies, colocalization, and rare variant analyses.</p>
RESULTS: Nine novel loci and 3 previously reported loci were identified to be associated with NT-proBNP levels. Novel structural variants were detected across 12 loci. Similar effect sizes were observed for both common and rare variants. Key genes such as BAG3 (10q26.11) and SLC39A8 (4q24) were identified through gene prioritization, with prior animal models supporting their therapeutic relevance. Rare variant analysis identified 6 masks with significant associations, specifically non-coding masks, suggesting regulatory modulation of NT-proBNP.</p>
CONCLUSIONS: This study identifies novel common, rare, and structural variants associated with NT-proBNP levels, highlighting the contribution of both coding and regulatory non-coding variation. These findings advance our understanding of the genetic architecture of NT-proBNP and may inform future cardiometabolic therapeutic strategies.</p>
9 Keywords
- Aged
- Female
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Natriuretic Peptide, Brain
- Peptide Fragments
- Polymorphism, Single Nucleotide
25 Authors
- Naman S. Shetty
- Akhil Pampana
- Mokshad Gaonkar
- Amrita Nayak
- Harshvir S. Bal
- Nirav Patel
- Nehal Vekariya
- J. Gustav Smith
- Alanna C. Morrison
- Bing Yu
- Bruce M. Psaty
- Eric Boerwinkle
- James S. Floyd
- Jerome I. Rotter
- Kent D. Taylor
- Leslie A. Lange
- Marguerite R. Irvin
- Mary Cushman
- Stephen S. Rich
- Ramachandran S. Vasan
- Thomas J. Wang
- Xiuqing Guo
- Peng Li
- Garima Arora
- Pankaj Arora
1 Application
| Application ID | Title |
|---|---|
| 58838 | Association of Genetic Variation in the Natriuretic Peptide System with Metabolic Risk Factors, Cardiovascular Events and Death |
Enabling scientific discoveries that improve human health