[Exploring the association between de novo mutations and non-syndromic cleft lip with or without palate based on whole exome sequencing of case-parent trios].

OBJECTIVE: To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design. METHODS: Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database. RESULTS: A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes. CONCLUSION: Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.

[Construction of professional competency model of center for disease prevention and control].

Objective: Analyze and contruct the post competency model of professionals in centers for disease prevention and control in Beijing, so as to provide information for cultivation and construction of public health personnel, and the human Resource Management in relevant institutions. Methods: Cross-sectional research method was used, and based on literature research, functional analysis and referring to Hay Group Competency Dictionary and McClellan Competency Dictionary, the post competency dictionary was established after the unified discussion of the subject group. Hierarchical cluster sampling method was used to investigate an online survey on competency factors of professionals in centers for Disease prevention and Control in Beijing, and factor analysis was conducted on the survey data. Results: The competency model of professionals in centers for disease prevention and control in Beijing was composed of six factors, which are Public health practical operation skills and norms, public health emergency response thinking and deductive and inductive ability, professional quality and professional ethics, communication, coordination ability and team spirit, medicine humanities knowledge and health management and guidance. Conclusions: This competency model is basically in line with the job responsibilities of professionals in centers for disease prevention and control in Beijing. However, it can only reflect the post competence and ability of the middle and junior technical personnel for practice, so which should belongs to the category of basic competence.

[Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees].

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION: Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.

[Progress in research of risk prediction of non-syndromic oral clefts using genetic information].

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.

[Progress in research of risk factors of iron deficiency and intervention in blood donors].

Long-term repeated regular blood donation may result in the loss and deficiency of iron. Epidemiological studies have indicated that blood donation frequency, demographical characteristics, and genetic factors are associated with iron deficiency. Our review summarizes the progress in research of etiology of iron deficiency in blood donors and intervention measures to provide evidence for the health management of non-remunerated blood donors in China.

[Summary of tools for assessment of public health emergency response capability].

With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.

[Family-based association tests for rare variants].

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.

[Progress in genetic epidemiology of non-syndromic cleft palate only].

One of the most common birth defects is cleft palate only (CPO) of which non-syndromic cleft palate only (NSCPO) accounts for 50%. NSCPO is a complex disease where multiple genes and environmental factors contribute to its risk. Unlike non-syndromic cleft lip with or without cleft palate (NSCL/P), previous genome-wide association studies only identified a few common genetic variations achieving genome-wide significance. This review summarizes the recent findings on genetic epidemiology of NSCPO. According to the current evidence, the candidate genes are divided into three categories: candidate genes with strong evidence, candidate genes with suggestive evidence, and candidate genes with inadequate evidence. The findings of epigenetic studies, the next generation sequencing studies, interaction analysis on NSCPO are also reviewed.

[A prospective cohort study on the association between smoking and blood pressure among middle-aged and elderly people].

Objective: Smoking is an important risk factor for cardiovascular events. However, data from some studies have shown that smoking is not associated with hypertension, and smokers may even have lower blood pressure than the non-smokers. Therefore, the association between smoking and blood pressure is yet to be further explored through longitudinal studies. This study explores the effect of smoking on blood pressure among people aged between forty five to eighty years old whose records are gathered from the China Health and Retirement Longitudinal Survey (CHARLS). Methods: Participants of CHARLS who completed all three surveys from both the national baseline investigation in 2011 and the follow-up surveys in 2013 and 2015, were enrolled. Multi-level linear regression was used to analyze the association between smoking and blood pressure, and Cox regression with time-varying variables was used to analyze the association between smoking and hypertension, after the adjustment for gender, age, education level, marital status, BMI, and alcohol consumption. Results: Subjects included in this study were with an average age of 58.8 years and 46.3% of them being male. After the adjustments of all the covariates, systolic and diastolic blood pressure of smokers appeared as 1.81 mmHg (95%CI: 0.55-3.07 mmHg, P<0.05) and 0.85 mmHg (95%CI: 0.10-1.60 mmHg, P<0.05), both higher than those of non-smokers, respectively. From the Cox regression analysis, data showed that smoking was not highly associated with the risk of hypertension development (HR=1.11, 95%CI: 0.89-1.38, P>0.05), statistically. Conclusions: Smoking seemed to be positively correlated with the elevation of blood pressure, among individuals aged between 45 and 80 years old. However, more evidence on the association between smoking and the risk of hypertension development needs to be further explored.