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Zeng P.,Xuzhou Medical College | Zhao Y.,Nanjing Medical University | Li H.,Center for Disease Control and Prevention of Pudong New Area | Wang T.,Xuzhou Medical College | Chen F.,Nanjing Medical University
BMC Medical Research Methodology

Background: In many medical studies the likelihood ratio test (LRT) has been widely applied to examine whether the random effects variance component is zero within the mixed effects models framework; whereas little work about likelihood-ratio based variance component test has been done in the generalized linear mixed models (GLMM), where the response is discrete and the log-likelihood cannot be computed exactly. Before applying the LRT for variance component in GLMM, several difficulties need to be overcome, including the computation of the log-likelihood, the parameter estimation and the derivation of the null distribution for the LRT statistic. Methods: To overcome these problems, in this paper we make use of the penalized quasi-likelihood algorithm and calculate the LRT statistic based on the resulting working response and the quasi-likelihood. The permutation procedure is used to obtain the null distribution of the LRT statistic. We evaluate the permutation-based LRT via simulations and compare it with the score-based variance component test and the tests based on the mixture of chi-square distributions. Finally we apply the permutation-based LRT to multilocus association analysis in the case-control study, where the problem can be investigated under the framework of logistic mixed effects model. Results: The simulations show that the permutation-based LRT can effectively control the type I error rate, while the score test is sometimes slightly conservative and the tests based on mixtures cannot maintain the type I error rate. Our studies also show that the permutation-based LRT has higher power than these existing tests and still maintains a reasonably high power even when the random effects do not follow a normal distribution. The application to GAW17 data also demonstrates that the proposed LRT has a higher probability to identify the association signals than the score test and the tests based on mixtures. Conclusions: In the present paper the permutation-based LRT was developed for variance component in GLMM. The LRT outperforms existing tests and has a reasonably higher power under various scenarios; additionally, it is conceptually simple and easy to implement. © 2015 Zeng et al.; licensee BioMed Central. Source

Xie Z.-Y.,Center for Disease Control and Prevention of Pudong New Area | Fu Y.-F.,Center for Disease Control and Prevention of Pudong New Area | Pu R.,Shanghai University | Ding Y.-B.,Shanghai University | And 4 more authors.
Academic Journal of Second Military Medical University

Objective: To study the transmission of hepatitis B virus (HBV) from mother to child and the related influencing factors, so as to provide evidence for HBV control. Methods: An epidemiological survey was conducted on 445 mother-infant pair participants with positive maternal HBsAg from 4 hospitals in Pudong New area of Shanghai. Peripheral blood samples of mothers and the umbilical cord blood samples of the infants were collected to detect the markers and DNA titer of HBV. HBsAg positive and HBV DNA positive in umbilical cord blood were defined as HBV positive in the infants. All the newborns received vaccination after birth according to the national regulation. Of the 445 participants, 104 newborns were followed for 7 months after birth, and the blood samples were collected and the markers and DNA titer of HBV were examined. HBsAg positive after 7 months was defined as immune failure. Results: The positive rate of HBV in the newborns was 8. 0% for mothers with positive HBsAg in our study. The HBV positive rate of newborns whose mothers were positive for both HBsAg and HBeAg was significantly higher than whose mothers were only HBsAg positive (26. 7% vs 1.8%, P<0. 05). The HBV positive rate was significantly higher in newborns whose mothers with HBV DNA >106 copies/mL compared with those with HBV DNA <106 copies/mL (23. 6% vs 2. 3%, P<0. 05). The immune failure rate of hepatitis B vaccine was 3. 8% 7 months after birth in our study, with all their mothers being positive for both HBsAg and HBeAg. Conclusion: The maternal HBeAg positivity and the high concentration of HBV DNA are the main risk factors of neonatal infection, and they may lead to non-response to hepatitis B vaccine. Source

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