Sex-biased genetic regulation of inflammatory proteins in the Dutch population.

Autor: Boahen CK; Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands., Abee H; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands., Ponce IR; Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands., Joosten LAB; Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands.; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacia, Cluj-Napoca-Napoca, Romania., Netea MG; Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands.; Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany., Kumar V; Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands. v.kumar@radboudumc.nl.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands. v.kumar@radboudumc.nl.; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, the Netherlands. v.kumar@radboudumc.nl.; Nitte (Deemed to Be University), Medical Sciences Complex, Nitte University Centre for Science Education and Research (NUCSER), Deralakatte, Mangalore, 575018, India. v.kumar@radboudumc.nl.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2024 Feb 08; Vol. 25 (1), pp. 154. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1186/s12864-024-10065-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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