| Title: | Sex differences in the genetic regulation of the human plasma proteome |
| Journal: | Nature Communications |
| Published: | 13 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40360480/ |
| DOI: | https://doi.org/10.1038/s41467-025-59034-4 |
| URL: | https://www.nature.com/articles/s41467-025-59034-4.pdf |
Publication 15352
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Abstract
Mechanisms underlying sex differences in the development and prognosis of many diseases remain largely elusive. Here, we systematically investigated sex differences in the genetic regulation of plasma proteome (>5800 protein targets) across two cohorts (30,307 females; 26,058 males). Plasma levels of two-thirds of protein targets differ significantly by sex. In contrast, genetic effects on protein targets are remarkably similar across sexes, with only 103 sex-differential protein quantitative loci (sd-pQTLs; for 2.9% and 0.3% of protein targets from antibody- and aptamer-based platforms, respectively). A third of those show evidence of sexual discordance, i.e., effects observed in one sex only (n = 30) or opposite effect directions (n = 1 for CDH15). Phenome-wide analyses of 365 outcomes in UK Biobank did not provide evidence that the identified sd-pQTLs accounted for sex-differential disease risk. Our results demonstrate similarities in the genetic regulation of protein levels by sex with important implications for genetically-guided drug target discovery and validation.</p>
11 Keywords
- Blood Proteins
- Cohort Studies
- Female
- Gene Expression Regulation
- Humans
- Male
- Middle Aged
- Proteome
- Quantitative Trait Loci
- Sex Characteristics
- Sex Factors
10 Authors
- Mine Koprulu
- Eleanor Wheeler
- Nicola D. Kerrison
- Spiros Denaxas
- Julia Carrasco-Zanini
- Chloe M. Orkin
- Harry Hemingway
- Nicholas J. Wareham
- Maik Pietzner
- Claudia Langenberg
1 Application
| Application ID | Title |
|---|---|
| 44448 | The genetic and environmental determinants of cardiometabolic and related disorders. |
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