EBioMedicine (Jan 2020)
Genetic risk for dengue hemorrhagic fever and dengue fever in multiple ancestries
- Guillaume Pare,
- Binod Neupane,
- Sasha Eskandarian,
- Eva Harris,
- Scott Halstead,
- Lionel Gresh,
- Guillermina Kuan,
- Angel Balmaseda,
- Luis Villar,
- Elsa Rojas,
- Jorge E. Osorio,
- Dang Duc Anh,
- Aruna Dharshan De Silva,
- Sunil Premawansa,
- Gayani Premawansa,
- Ananda Wijewickrama,
- Ivette Lorenzana,
- Leda Parham,
- Cynthia Rodriguez,
- Ildefonso Fernandez-Salas,
- Rosa Sanchez-Casas,
- Esteban E. Diaz-Gonzalez,
- Khin Saw Aye,
- Win Lai May,
- Min Thein,
- Filemon Bucardo,
- Yaoska Reyes,
- Patricia Blandon,
- Kenji Hirayama,
- Lan Weiss,
- Pardeep Singh,
- Jennifer Newton,
- Mark Loeb
Affiliations
- Guillaume Pare
- Department of Pathology and Molecular Medicine, McMaster University, Ontario L8N 3Z5, Canada; Department of Health Research, Methods, Evidence, and Impact, Canada
- Binod Neupane
- Department of Pathology and Molecular Medicine, McMaster University, Ontario L8N 3Z5, Canada
- Sasha Eskandarian
- Department of Pathology and Molecular Medicine, McMaster University, Ontario L8N 3Z5, Canada
- Eva Harris
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, United States
- Scott Halstead
- Department of Preventive Medicine and Biometrics, Uniformed University of the Health Sciences, Bethesda, MD, United States
- Lionel Gresh
- Sustainable Sciences Institute, Managua, Nicaragua
- Guillermina Kuan
- Health Center Sócrates Flores Vivas, Ministry of Health, Managua, Nicaragua
- Angel Balmaseda
- Sustainable Sciences Institute, Managua, Nicaragua; Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua
- Luis Villar
- Clinical Epidemiology Unit, Universidad Industrial de Santander, Bucaramanga, Colombia
- Elsa Rojas
- Centro de Atención y Diagnóstico de Enfermedades Infecciosas, Bucaramanga, Colombia
- Jorge E. Osorio
- University of Wisconsin, Wisconsin, United States
- Dang Duc Anh
- National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
- Aruna Dharshan De Silva
- Genetech Research Institute, Sri Lanka
- Sunil Premawansa
- Department of Zoology and Environmental Sciences, University of Colombo, Sri Lanka
- Gayani Premawansa
- Genetech Research Institute, Sri Lanka
- Ananda Wijewickrama
- Genetech Research Institute, Sri Lanka
- Ivette Lorenzana
- Department of National Autonomous University of Honduras, Tegucigalpa, Honduras
- Leda Parham
- Department of National Autonomous University of Honduras, Tegucigalpa, Honduras
- Cynthia Rodriguez
- Department of National Autonomous University of Honduras, Tegucigalpa, Honduras
- Ildefonso Fernandez-Salas
- Universidad Autonoma de Nuevo Leon, Mexico
- Rosa Sanchez-Casas
- Universidad Autonoma de Nuevo Leon, Mexico
- Esteban E. Diaz-Gonzalez
- Universidad Autonoma de Nuevo Leon, Mexico
- Khin Saw Aye
- Medical Research, Ministry of Health, Myanmar
- Win Lai May
- Medical Research, Ministry of Health, Myanmar
- Min Thein
- Medical Research, Ministry of Health, Myanmar
- Filemon Bucardo
- The Faculty of Medical Sciences at the National Autonomous University of León, Nicaragua
- Yaoska Reyes
- The Faculty of Medical Sciences at the National Autonomous University of León, Nicaragua
- Patricia Blandon
- The Faculty of Medical Sciences at the National Autonomous University of León, Nicaragua
- Kenji Hirayama
- Department of Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagaski, Japan
- Lan Weiss
- Department of Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagaski, Japan; Department of Immunology and Microbiology, Pasteur Institute, Ho Chi Minh City, Vietnam
- Pardeep Singh
- Department of Pathology and Molecular Medicine, McMaster University, Ontario L8N 3Z5, Canada
- Jennifer Newton
- Department of Pathology and Molecular Medicine, McMaster University, Ontario L8N 3Z5, Canada
- Mark Loeb
- Department of Pathology and Molecular Medicine, McMaster University, Ontario L8N 3Z5, Canada; Department of Health Research, Methods, Evidence, and Impact, Canada; Institute for Infectious Diseases Research, McMaster University Hamilton, Canada; Corresponding author at: Department of Pathology and Molecular Medicine, McMaster University Hamilton, Ontario L8N 3Z5, Canada.
- Journal volume & issue
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Vol. 51
Abstract
Background: Genetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations. Methods: We conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls. Findings: The risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other. Interpretation: There is a strong genetic effect that predisposes to risk of DHF/DSS and DF. The genetic risk for DHF/DSS is higher than that for DF when compared to controls, and this effect persists across multiple ancestries. Keywords: Dengue, Genetics, Risk, GWAS, Ancestry
