| Title: | Sex-specific genetic architecture of blood pressure |
| Journal: | Nature Medicine |
| Published: | 8 Mar 2024 |
| DOI: | https://doi.org/10.1038/s41591-024-02858-2 |
Publication 8524
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
The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associated loci. Among associated loci, 412 were female-specific (Pfemale ≤ 5 × 10−8; Pmale > 5 × 10−8) and 142 were male-specific (Pmale ≤ 5 × 10−8; Pfemale > 5 × 10−8); these sex-specific loci were enriched for hormone-related transcription factors, in particular, estrogen receptor 1. Analyses of gene-by-sex interactions and sexually dimorphic effects identified four genomic regions, showing female-specific associations with diastolic BP or pulse pressure, including the chromosome 13q34-COL4A1/COL4A2 locus. Notably, female-specific pulse pressure-associated loci exhibited enriched acetylated histone H3 Lys27 modifications in arterial tissues and a female-specific association with fibromuscular dysplasia, a female-biased vascular disease; colocalization signals included Chr13q34: COL4A1/COL4A2, Chr9p21: CDKN2B-AS1 and Chr4q32.1: MAP9 regions. Sex-specific and sex-biased polygenic associations of BP traits were associated with multiple cardiovascular traits. These findings suggest potentially clinically significant and BP sex-specific pleiotropic effects on cardiovascular diseases.</p>
7 Authors
- Min-Lee Yang
- Chang Xu
- Trisha Gupte
- Thomas J. Hoffmann
- Carlos Iribarren
- Xiang Zhou
- Santhi K. Ganesh
Enabling scientific discoveries that improve human health