Sex-biased genetic regulation of inflammatory proteins in the Dutch population
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 p...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-024-10065-z |
| _version_ | 1827328530273271808 |
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| author | Collins K. Boahen Hannah Abee Isis Ricaño Ponce Leo A. B. Joosten Mihai G. Netea Vinod Kumar |
| author_facet | Collins K. Boahen Hannah Abee Isis Ricaño Ponce Leo A. B. Joosten Mihai G. Netea Vinod Kumar |
| author_sort | Collins K. Boahen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T15:19:02Z |
| format | Article |
| id | doaj.art-7271068d610c4509997707114808a248 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-07T15:19:02Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
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| series | BMC Genomics |
| spelling | doaj.art-7271068d610c4509997707114808a2482024-03-05T17:47:14ZengBMCBMC Genomics1471-21642024-02-0125112010.1186/s12864-024-10065-zSex-biased genetic regulation of inflammatory proteins in the Dutch populationCollins K. Boahen0Hannah Abee1Isis Ricaño Ponce2Leo A. B. Joosten3Mihai G. Netea4Vinod Kumar5Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical CenterAbstract 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.https://doi.org/10.1186/s12864-024-10065-zSex-stratified genetic analysisInflammationpQTLGWASBiomarkers |
| spellingShingle | Collins K. Boahen Hannah Abee Isis Ricaño Ponce Leo A. B. Joosten Mihai G. Netea Vinod Kumar Sex-biased genetic regulation of inflammatory proteins in the Dutch population BMC Genomics Sex-stratified genetic analysis Inflammation pQTL GWAS Biomarkers |
| title | Sex-biased genetic regulation of inflammatory proteins in the Dutch population |
| title_full | Sex-biased genetic regulation of inflammatory proteins in the Dutch population |
| title_fullStr | Sex-biased genetic regulation of inflammatory proteins in the Dutch population |
| title_full_unstemmed | Sex-biased genetic regulation of inflammatory proteins in the Dutch population |
| title_short | Sex-biased genetic regulation of inflammatory proteins in the Dutch population |
| title_sort | sex biased genetic regulation of inflammatory proteins in the dutch population |
| topic | Sex-stratified genetic analysis Inflammation pQTL GWAS Biomarkers |
| url | https://doi.org/10.1186/s12864-024-10065-z |
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