Genetic Influences on Incidence and Case-Fatality of Infectious Disease
Genetic Influences on Incidence and Case-Fatality of Infectious Disease
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DOI：
10.1371/journal.pone.0010603
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发表时间：
2010-05-14
期刊：
影响因子：
3.7
通讯作者：
Sorensen, Thorkild I. A.
中科院分区：
文献类型：
--
作者：
Petersen, Liselotte;Andersen, Per Kragh;Sorensen, Thorkild I. A.
背景：家庭、双胞胎和收养研究表明，遗传易感性有助于传染病的家族聚集或因感染而死亡。我们分别估计了遗传和共同环境对获得感染风险（发病率）和死亡（病死率）的影响。方法：通过感染住院率和被收养者及其同父异母和同父异母兄弟姐妹病死率之间的关联来估计遗传影响。对被收养者及其收养的兄弟姐妹进行了家庭环境影响调查。在1924年至1947年期间丹麦批准的14,425例非家庭收养中，我们选择了1,603名被收养者，他们在1977年至1993年期间因感染住院和/或死于感染。他们的兄弟姐妹被认为易受感染，并与随机选择的1,348名1993年被收养者的非易感兄弟姐妹进行比较，这些被收养者在观察期间没有因感染而住院。给出的风险比基于Cox回归模型。结果：9971例确诊手足中有2829例因感染住院。易感者的传染病风险在生物学（1.18；95%置信限1.03-1.36）和收养的兄弟姐妹（1.23;0.98-1.53）中均高于非易感者。在生物学上完全相同的兄弟姐妹中，感染致命结果的风险显著增加（9.36;2.94-29.8），但在生物学上同父异母的兄弟姐妹或收养的兄弟姐妹中没有观察到这种关联。结论：感染风险似乎受到遗传决定的感染易感性和家庭环境的微弱影响，而对致命结果的风险似乎有很强的非加性遗传影响。
Background: Family, twin and adoption studies suggest that genetic susceptibility contributes to familial aggregation of infectious diseases or to death from infections. We estimated genetic and shared environmental influences separately on the risk of acquiring an infection (incidence) and on dying from it (case fatality).Methods: Genetic influences were estimated by the association between rates of hospitalization for infections and between case-fatality rates of adoptees and their biological full- and half-siblings. Familial environmental influences were investigated in adoptees and their adoptive siblings. Among 14,425 non-familial adoptions, granted in Denmark during the period 1924-47, we selected 1,603 adoptees, who had been hospitalized for infections and/or died with infection between 1977 and 1993. Their siblings were considered predisposed to infection, and compared with non-predisposed siblings of randomly selected 1,348 adoptees alive in 1993 and not hospitalized for infections in the observation period. The risk ratios presented were based on a Cox regression model.Results: Among 9971 identified siblings, 2829 had been hospitalised for infections. The risk of infectious disease was increased among predisposed compared with non-predisposed in both biological (1.18; 95% confidence limits 1.03-1.36) and adoptive siblings (1.23; 0.98-1.53). The risk of a fatal outcome of the infections was strongly increased (9.36; 2.94-29.8) in biological full siblings, but such associations were not observed for the biological half siblings or for the adoptive siblings.Conclusion: Risk of getting infections appears to be weakly influenced by both genetically determined susceptibility to infection and by family environment, whereas there appears to be a strong non-additive genetic influence on risk of fatal outcome.