Back to Search
Start Over
Sex-specific genetic architecture of blood pressure
- Source :
- Nature Medicine; March 2024, Vol. 30 Issue: 3 p818-828, 11p
- Publication Year :
- 2024
-
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/COL4A2locus. 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-AS1and Chr4q32.1: MAP9regions. 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.
Details
- Language :
- English
- ISSN :
- 10788956 and 1546170X
- Volume :
- 30
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Nature Medicine
- Publication Type :
- Periodical
- Accession number :
- ejs65720281
- Full Text :
- https://doi.org/10.1038/s41591-024-02858-2