tetano
Editor, Senior Moderator
Genome Med
. 2026 Jul 2.
doi: 10.1186/s13073-026-01703-0. Online ahead of print.
Identification and functional characterization of regulatory variants in DPP9 associated with COVID-19 severity
Gaëlle Farah[SUP] 1 2 [/SUP], Magali Torres[SUP] 1 2 [/SUP], Leo Henches[SUP] 3 [/SUP], Hugues Aschard[SUP] 3 4 [/SUP], Jade Ghosn[SUP] 5 6 [/SUP], Xavier Duval[SUP] 5 7 [/SUP]; Milieu Intérieur Consortium; French COVID Cohort Study Group; Pascal Rihet[SUP] 1 [/SUP], Salvatore Spicuglia[SUP] 8 9 [/SUP], Sandrine Marquet[SUP] 10 11 [/SUP]
Collaborators, Affiliations
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a wide-range of clinical outcomes, which have been extensively studied through genome-wide association studies (GWAS).
Methods: Starting from lead genetic variants associated with COVID-19 infection and severity, we identified a subset of non-coding candidate variants with potential regulatory functions. We combined bioinformatics analysis and functional screening in three cell lines to provide evidence for regulatory activity. We then performed a genetic study to test the association of our selected candidates with disease susceptibility followed by the functional validation of the risk haplotype.
Results: We prioritized two DPP9 variants within a haplotype that increases the risk of severe COVID-19. This haplotype exhibited increased regulatory activity and altered transcription factor binding, suggesting its role in influencing COVID-19 severity by modulating DPP9 expression in immune and lung cell types.
Conclusions: The interest of our study lies in the functional characterization of regulatory variants responsible for increased levels of DPP9 and lung damage observed in patients with severe COVID-19. These findings advance our understanding of genetic risk factors for COVID-19 and highlight functional SNPs that may guide future therapeutic research.
Keywords: DPP9; Bioinformatics priorization; COVID-19; Functional validation; Genetic association; Haplotype; Regulatory variants; Severe disease; Transcription factors.
. 2026 Jul 2.
doi: 10.1186/s13073-026-01703-0. Online ahead of print.
Identification and functional characterization of regulatory variants in DPP9 associated with COVID-19 severity
Gaëlle Farah[SUP] 1 2 [/SUP], Magali Torres[SUP] 1 2 [/SUP], Leo Henches[SUP] 3 [/SUP], Hugues Aschard[SUP] 3 4 [/SUP], Jade Ghosn[SUP] 5 6 [/SUP], Xavier Duval[SUP] 5 7 [/SUP]; Milieu Intérieur Consortium; French COVID Cohort Study Group; Pascal Rihet[SUP] 1 [/SUP], Salvatore Spicuglia[SUP] 8 9 [/SUP], Sandrine Marquet[SUP] 10 11 [/SUP]
Collaborators, Affiliations
- PMID: 42393744
- DOI: 10.1186/s13073-026-01703-0
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a wide-range of clinical outcomes, which have been extensively studied through genome-wide association studies (GWAS).
Methods: Starting from lead genetic variants associated with COVID-19 infection and severity, we identified a subset of non-coding candidate variants with potential regulatory functions. We combined bioinformatics analysis and functional screening in three cell lines to provide evidence for regulatory activity. We then performed a genetic study to test the association of our selected candidates with disease susceptibility followed by the functional validation of the risk haplotype.
Results: We prioritized two DPP9 variants within a haplotype that increases the risk of severe COVID-19. This haplotype exhibited increased regulatory activity and altered transcription factor binding, suggesting its role in influencing COVID-19 severity by modulating DPP9 expression in immune and lung cell types.
Conclusions: The interest of our study lies in the functional characterization of regulatory variants responsible for increased levels of DPP9 and lung damage observed in patients with severe COVID-19. These findings advance our understanding of genetic risk factors for COVID-19 and highlight functional SNPs that may guide future therapeutic research.
Keywords: DPP9; Bioinformatics priorization; COVID-19; Functional validation; Genetic association; Haplotype; Regulatory variants; Severe disease; Transcription factors.