| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
EBioMedicine, Vol 51, Iss , Pp - (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2019.11.045 |
| Popis: |
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 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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