Sex-biased genetic regulation of inflammatory proteins in the Dutch population
BMC Genomics, 2024
Boahen C., Abee H., Ponce I., Joosten L., Netea M., Kumar V.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Wider Proteomics Studies | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background
Significant differences in immune responses, prevalence or susceptibility of diseases and treatment responses have been described between males and females. Despite this, sex-differentiation analysis of the genetic architecture of inflammatory proteins is largely unexplored. We performed sex-stratified meta-analysis after protein quantitative trait loci (pQTL) mapping using inflammatory biomarkers profiled using targeted proteomics (Olink inflammatory panel) of two population-based cohorts of Europeans.
Results
Even though, around 67% of the pQTLs demonstrated shared effect between sexes, colocalization analysis identified two loci in the males (LINC01135 and ITGAV) and three loci (CNOT10, SRD5A2, and LILRB5) in the females with evidence of sex-dependent modulation by pQTL variants. Furthermore, we identified pathways with relevant functions in the sex-biased pQTL variants. We also showed through cross-validation that the sex-specific pQTLs are linked with sex-specific phenotypic traits.
Conclusion
Our study demonstrates the relevance of genetic sex-stratified analysis in the context of genetic dissection of protein abundances among individuals and reveals that, sex-specific pQTLs might mediate sex-linked phenotypes. Identification of sex-specific pQTLs associated with sex-biased diseases can help realize the promise of individualized treatment.