title: African genetic ancestry is associated with a protective effect on Dengue severity in colombian populations.
abstract: The wide variation in severity displayed during Dengue Virus (DENV) infection may be influenced by host susceptibility. In several epidemiological approaches, differences in disease outcomes have been found between some ethnic groups, suggesting that human genetic background has an important role in disease severity. In the Caribbean, It has been reported that populations of African descent present considerable less frequency of severe forms compared with Mestizo and White self-reported groups. Admixed populations offer advantages for genetic epidemiology studies due to variation and distribution of alleles, such as those involved in disease susceptibility, as well to provide explanations of individual variability in clinical outcomes. The current study analysed three Colombian populations, which like most of Latin American populations, are made up of the product of complex admixture processes between European, Native American and African ancestors; having as a main goal to assess the effect of genetic ancestry, estimated with 30 Ancestry Informative Markers (AIMs), on DENV infection severity. We found that African ancestry has a protective effect against severe outcomes under several systems of clinical classification: Severe Dengue (OR: 0.963 for every 1% increase in African ancestry, 95% confidence interval (0.934-0.993), p-value: 0.016), Dengue Haemorrhagic Fever (OR: 0.969, 95% CI (0.947-0.991), p-value: 0.006), and occurrence of haemorrhages (OR: 0.971, 95% CI (0.952-0.989), p-value: 0.002). Conversely, decrease from 100% to 0% African ancestry significantly increases the chance of severe outcomes: OR is 44-fold for Severe Dengue, 24-fold for Dengue Haemorrhagic Fever, and 20-fold for occurrence of haemorrhages. Furthermore, several warning signs also showed statistically significant association given more evidences in specific stages of DENV infection. These results provide consistent evidence in order to infer statistical models providing a framework for future genetic epidemiology and clinical studies.
authors.affiliation: Grupo GENMOL, Universidad de Antioquia. Medellín, Colombia. Electronic address: juan.chacon-duque.13@ucl.ac.uk.
authors.forename: Juan Camilo
authors.initials: JC
authors.lastname: Chacón-Duque
authors.affiliation: Department of Genetics, Evolution and Environment, University College London (UCL), London, UK.
authors.forename: Kaustubh
authors.initials: K
authors.lastname: Adhikari
authors.affiliation: Grupo GENMOL, Universidad de Antioquia. Medellín, Colombia.
authors.forename: Efren
authors.initials: E
authors.lastname: Avendaño
authors.affiliation: Grupo GENMOL, Universidad de Antioquia. Medellín, Colombia.
authors.forename: Omer
authors.initials: O
authors.lastname: Campo
authors.affiliation: Instituto Colombiano de Medicina Tropical "Antonio Roldán Betancur" (ICMT), Universidad CES, Sabaneta, Colombia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ramirez
authors.affiliation: Grupo GENMOL, Universidad de Antioquia. Medellín, Colombia.
authors.forename: Winston
authors.initials: W
authors.lastname: Rojas
authors.affiliation: Department of Genetics, Evolution and Environment, University College London (UCL), London, UK.
authors.forename: Andrés
authors.initials: A
authors.lastname: Ruiz-Linares
authors.affiliation: Instituto Colombiano de Medicina Tropical "Antonio Roldán Betancur" (ICMT), Universidad CES, Sabaneta, Colombia.
authors.forename: Berta Nelly
authors.initials: BN
authors.lastname: Restrepo
authors.affiliation: Grupo GENMOL, Universidad de Antioquia. Medellín, Colombia.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bedoya
mesh_terms: D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003105:Colombia / Q000208:ethnology; D003715:Dengue / Q000175:diagnosis* / Q000235:genetics*; D003716:Dengue Virus; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: DENV infection; Dengue severity; Genetic ancestry; Susceptibility