| Title: | Sex-specific genetic architecture of blood pressure |
| Journal: | Nature Medicine |
| Published: | 8 Mar 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38459180/ |
| DOI: | https://doi.org/10.1038/s41591-024-02858-2 |
| Citations: | 1 (1 in last 2 years) as of 8 Aug 2024 |
Publication 8524
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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>
11 Keywords
- Blood Pressure
- Cardiovascular Diseases
- Female
- Genetic Predisposition to Disease
- Genome
- Genome-Wide Association Study
- Humans
- Male
- Microtubule-Associated Proteins
- Phenotype
- Polymorphism, Single Nucleotide
7 Authors
- Min-Lee Yang
- Chang Xu
- Trisha Gupte
- Thomas J. Hoffmann
- Carlos Iribarren
- Xiang Zhou
- Santhi K. Ganesh
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