Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores: evidence from the China Kadoorie Biobank / 中华医学杂志(英文版)

BACKGROUND@#Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population.@*METHODS@#Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately.@*RESULTS@#In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model.@*CONCLUSIONS@#In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.

Frequency of bowel movements and risk of Parkinson’s disease: a prospective cohort study in adults in China / 中华流行病学杂志

Objective@#To evaluate the association between the frequency of bowel movement (BMF) and the risk of Parkinson’s disease (PD).@*Methods@#In this study, 510 134 participants from the China Kadoorie Biobank (CKB) were included after excluding those who reported to had been diagnosed with cancer at baseline survey. The baseline survey was conducted from 2004 to 2008. The study used the data from the baseline survey and follow-up until December 31, 2016. Cox proportional hazards regression models were used to estimate the HRs and the 95%CIs of risk of PD diagnosis with BMF.@*Results@#During an average follow-up period of (9.9±1.9) years, 808 participants were diagnosed with PD. Compared with participants who had bowel movements every day, the multivariable-adjusted HR (95%CI) for those who had bowel movements<3 times/week, once every 2-3 days, and>1 time/day were 3.62 (2.88-4.54), 2.13 (1.74-2.60), and 0.81 (0.63-1.05), respectively. The linear trend test results of the association between BMF and risk of PD diagnosis was significant (P<0.001). Compared with the participants who had bowel movements ≥1 time/day, the multivariable-adjusted HR (95%CI) for those who had bowel movements<1 time/day was 3.13 (2.32-4.23) within the 5 years of follow- up and was 2.48 (2.05-3.01) beyond the 5 years of follow-up. The gender specific results were similar. The association of BMF<1 time/day with risk of PD diagnosis was stronger in older participants.@*Conclusions@#The participants with low BMF at baseline survey would have higher risk for PD diagnosis in the subsequent 10 years on average. Since abnormal decrease of BMF is easy to be found, programs could be set up for the early screening of PD in older people, along with other early symptoms of PD.

New progress in epidemiological research / 中华流行病学杂志

Epidemiology is a discipline integrating methodology and applied science, whose mission is to prevent and control diseases and promote health. This review introduces the new progress of epidemiology from five aspects: communicable diseases, chronic diseases, systems epidemiology, implementation research and big data of health care. New projects and constantly emerging technologies in the field of infectious diseases are inspiring, while more attention should be paid to the environmental factors of pathogen variation. In the field of chronic diseases, there is an urgent need to study the multimorbidity of the elderly. The role of infectious inducers and human microbiota in the occurrence and development of chronic diseases has been gradually revealed. Systems epidemiology, which is of great significance to achieve precision prevention is a new branch and an important supplement of modern epidemiology. Implementation research, is a bridge connecting basic scientific research and public health practice and will provide evidence to support the effective implementation of the Health China Action Plan. The development of health care big data is based on digital public health, which provides a broad research platform and abundant data resources for epidemiology, and will promote the fundamental transformation of the service and management mode of public health.

Family History, Tobacco Smoking, and Risk of Ischemic Stroke / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Both genetic factors and smoking are associated with ischemic stroke (IS) risk. However, little is known about the potential interaction of these factors. We aimed to assess whether smoking and a positive family history interact to increase the risk of IS. METHODS: The nationwide prospective study recruited 210,000 men and 300,000 women in 2004 to 2008 at ages 30 to 79 years. During 9.7 years of follow-up, we documented 16,923 and 20,656 incident IS cases in men and women without major chronic diseases at baseline, respectively. Multivariable Cox regression models were used to examine associations between family history and IS. Likelihood ratio tests were used to test the smoking-family history interactions on IS. RESULTS: About 67.8% (n=135,168) of men ever smoked regularly compared with 2.7% (n=7,775) of women. Among men, a significant interaction between family history and smoking on IS was observed (P for interaction=0.03), with more pronounced association between family history and IS among ever-regular smokers (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.16 to 1.27) than among never-smokers (HR, 1.11; 95% CI, 1.01 to 1.23). The association between family history and IS among ex-smokers after more than 10 years of cessation (HR, 1.01; 95% CI, 0.85 to 1.20) appeared similar to that among never-smokers. Among women, a similar but not significant interaction between family history and smoking on IS was observed. Ever-regular smokers who had a family history of stroke had the highest risk of IS. CONCLUSIONS: Among Chinese men, the association of family history with IS was accentuated by smoking, and such accentuation tended to be lowered by cessation.

Association between the frequency of bowel movements and the risk of colorectal cancer in Chinese adults / 中华流行病学杂志

Objective@#To examine the association between the frequencies of bowel movement (BMF) and the risk of colorectal cancer (CRC).@*Methods@#In this study, 510 134 participants from the China Kadoorie Biobank (CKB) were included, after excluding those who reported as having been diagnosed with cancer at the baseline survey. The baseline survey was conducted from June 2004 to July 2008. The present study included data from baseline and follow-up until December 31, 2016. We used the Cox proportional hazards regression models to estimate the HR and the 95%CI of incident CRC with BMF.@*Results@#During an average follow-up period of 9.9 years, 3 056 participants were documented as having developed colorectal cancer. In the site-specific analysis, 1 548 colon cancer and 1 475 rectal cancer were included. Compared with participants who had bowel movements on the daily base, the multivariable-adjusted HR (95%CI) for those who had more than once of BMF were 1.24 (1.12-1.39) for CRC, 1.12 (0.95-1.31) for colon cancer, and 1.37 (1.18-1.59) for rectal cancer. We further examined the association between BMF and CRC, according to the stages of follow-up, the corresponding HR (95%CI) for CRC, colon and rectal cancer were 1.59 (1.36-1.86), 1.43 (1.14- 1.80), and 1.76 (1.41-2.19) for the first five years, while such associations became statistically insignificant in the subsequent follow-up (P for all interactions were <0.05), as time went on. As for CRC, colon or rectal cancers among participants who had lower bowel movements, the risks were not significantly different from those who had bowel movements everyday.@*Conclusions@#Participants who had BMF more than once a day, appeared an increased risk of CRC in the subsequent five years. Since abnormal increase of bowel movements is easily recognizable, programs should be set up on health self- management and early screening for CRC.

Association between central obesity and risk for heart disease in adults in China: a prospective study / 中华流行病学杂志

Objective To understand the association between central obesity,assessed by waist circumference,and the risks for ischemic heart disease (IHD),major coronary event (MCE),and IHD death.Methods After excluding participants with heart disease,stroke,cancer,COPD,and diabetes at baseline survey,we included a total of 428 595 participants from the China Kadoorie Biobank for the analysis.The baseline survey was conducted from June 2004 to July 2008.We used Cox proportional hazards model to estimate the hazard ratio (HR) and 95％CI.Results During an average 9.1 years of follow-up (3 803 637 person-years),we documented 26 900 incident cases of IHD,4 320 cases of MCE,and 2 787 of deaths from IHD.After adjustment for possible confounders and BMI,central obesity was found to be associated with increased risks for IHD,MCE,and IHD death.The adjusted HRs (for the participants who had waist circumference of 85.0-89.9 cm in men and 80.0-84.9 cm in women were 1.13 (95％CI:1.09-1.17) for IHD,1.15 (95％CI:1.05-1.26) for MCE and 1.11 (95％ CI:0.98-1.24) for IHD death.The respective HRs for those central obese participants (men ≥90.0 cm,women ≥85.0 cm) were 1.29 (95％ CI:1.24-1.34),1.30 (95％ CI:1.17 1.44) and 1.32 (95％CI:1.16 1.5 1).Further stratification analysis according to BMI showed that the risks for incident IHD,MCE,and IHD death increased along with the increase of waist circumference even in the participants with normal weight.Conclusion This large-scale prospective study revealed that central obesity was an independent risk factor for IHD in adults in China,and the risk of IHD would increase with the increase of waist circumference.

Association between central obesity and risk for heart disease in adults in China: a prospective study / 中华流行病学杂志

Objective To understand the association between central obesity,assessed by waist circumference,and the risks for ischemic heart disease (IHD),major coronary event (MCE),and IHD death.Methods After excluding participants with heart disease,stroke,cancer,COPD,and diabetes at baseline survey,we included a total of 428 595 participants from the China Kadoorie Biobank for the analysis.The baseline survey was conducted from June 2004 to July 2008.We used Cox proportional hazards model to estimate the hazard ratio (HR) and 95％CI.Results During an average 9.1 years of follow-up (3 803 637 person-years),we documented 26 900 incident cases of IHD,4 320 cases of MCE,and 2 787 of deaths from IHD.After adjustment for possible confounders and BMI,central obesity was found to be associated with increased risks for IHD,MCE,and IHD death.The adjusted HRs (for the participants who had waist circumference of 85.0-89.9 cm in men and 80.0-84.9 cm in women were 1.13 (95％CI:1.09-1.17) for IHD,1.15 (95％CI:1.05-1.26) for MCE and 1.11 (95％ CI:0.98-1.24) for IHD death.The respective HRs for those central obese participants (men ≥90.0 cm,women ≥85.0 cm) were 1.29 (95％ CI:1.24-1.34),1.30 (95％ CI:1.17 1.44) and 1.32 (95％CI:1.16 1.5 1).Further stratification analysis according to BMI showed that the risks for incident IHD,MCE,and IHD death increased along with the increase of waist circumference even in the participants with normal weight.Conclusion This large-scale prospective study revealed that central obesity was an independent risk factor for IHD in adults in China,and the risk of IHD would increase with the increase of waist circumference.