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.

中文翻译：

---

登革出血热和多发性登革热的遗传风险。

背景技术登革出血热/登革热综合征（DHF / DSS）和登革热（DF）的遗传风险因素是有限的，特别是在不同人群中遗传风险的数据稀少。方法我们在7 460名拉丁美洲，南亚和东南亚祖先的参与者的衍生和验证样本中进行了全基因组关联研究（GWAS）。然后，我们为三个祖先的每个验证队列中的每个参与者制定了加权多基因风险评分（PRS），以预测与DF相比的DHF / DSS风险，与对照相比的DHF / DSS和与对照相比的DF。结果与验证组相比，DF，第四个PRS四分位数与第一个四分位数相比，DF的风险显着增加，比值比[OR]为1.84（95％CI 1.47至2.31）（195个SNP）。与对照组相比，DHF / DSS的风险增加（OR = 3.94; 95％CI 2.84至5.45）（278个SNP），与DF相比，与对照组相比的风险（OR = 1.97; 95％CI 1.63至2.39）（ 251个SNP）。跨比较，随着PRS四分位数的增加，风险以剂量依赖性方式增加。对于在祖先内建立并应用于相同或不同祖先的PRS以及对于一种结果（DHF / DSS或DF）建立并应用于另一结果的PRS，存在重要的关联。解释有很强的遗传效应，易患DHF / DSS和DF。与对照相比，DHF / DSS的遗传风险高于DF的遗传风险，并且这种效应在多个祖先中持续存在。39）（251个SNP）。跨比较，随着PRS四分位数的增加，风险以剂量依赖性方式增加。对于在祖先内建立并应用于相同或不同祖先的PRS以及对于一种结果（DHF / DSS或DF）建立并应用于另一结果的PRS，存在重要的关联。解释有很强的遗传效应，易患DHF / DSS和DF。与对照相比，DHF / DSS的遗传风险高于DF的遗传风险，并且这种效应在多个祖先中持续存在。39）（251个SNP）。跨比较，随着PRS四分位数的增加，风险以剂量依赖性方式增加。对于在祖先内建立并应用于相同或不同祖先的PRS以及对于一种结果（DHF / DSS或DF）建立并应用于另一结果的PRS，存在重要的关联。解释有很强的遗传效应，易患DHF / DSS和DF。与对照相比，DHF / DSS的遗传风险高于DF的遗传风险，并且这种效应在多个祖先中持续存在。解释有很强的遗传效应，易患DHF / DSS和DF。与对照相比，DHF / DSS的遗传风险高于DF的遗传风险，并且这种效应在多个祖先中持续存在。解释有很强的遗传效应，易患DHF / DSS和DF。与对照相比，DHF / DSS的遗传风险高于DF的遗传风险，并且这种效应在多个祖先中持续存在。