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.

Family history and risk of coronary heart disease / 中华流行病学杂志

Objective To evaluate the association of family history with risk of major coronary events (MCE) and ischemic heart disease (IHD).Methods After excluding participants with heart disease,stroke or cancer at baseline survey,a total of 485 784 participants from the China Kadoorie Biobank,who had no missing data on critical variables,were included in the analysis.Cox regression analysis was used to estimate the hazard ratios (HR) and 95％CI.Subgroup analyses were performed according to the baseline characteristics.Results During a median of 7.2 years of follow-up,we documented 3 934 incident cases of MCE and 24 537 cases of IHD.In multivariableadjusted models,family history was significantly associated with risk of MCE and IHD.The adjusted HRs (95％CI) were 1.41 (1.19-1.65) and 1.25 (1.18-1.33),respectively.History of disease among siblings was more strongly associated with early-onset MCE than parental history (HR=2.97,95％CI:1.80-4.88).Moreover,the association of family history with MCE and IHD was stronger in persons who were overweight or obesive,and the association between family history and MEC was stronger in smokers.Conclusion This large-scale,prospective study indicated that family history was an independent risk factor for MCE and IHD in China.The intervention targeting major known lifestyle risk factors and the management of chronic diseases should be strengthened for Chinese population,especially for the individuals with family history were at high risk.

Family history and risk of coronary heart disease / 中华流行病学杂志

Objective To evaluate the association of family history with risk of major coronary events (MCE) and ischemic heart disease (IHD).Methods After excluding participants with heart disease,stroke or cancer at baseline survey,a total of 485 784 participants from the China Kadoorie Biobank,who had no missing data on critical variables,were included in the analysis.Cox regression analysis was used to estimate the hazard ratios (HR) and 95％CI.Subgroup analyses were performed according to the baseline characteristics.Results During a median of 7.2 years of follow-up,we documented 3 934 incident cases of MCE and 24 537 cases of IHD.In multivariableadjusted models,family history was significantly associated with risk of MCE and IHD.The adjusted HRs (95％CI) were 1.41 (1.19-1.65) and 1.25 (1.18-1.33),respectively.History of disease among siblings was more strongly associated with early-onset MCE than parental history (HR=2.97,95％CI:1.80-4.88).Moreover,the association of family history with MCE and IHD was stronger in persons who were overweight or obesive,and the association between family history and MEC was stronger in smokers.Conclusion This large-scale,prospective study indicated that family history was an independent risk factor for MCE and IHD in China.The intervention targeting major known lifestyle risk factors and the management of chronic diseases should be strengthened for Chinese population,especially for the individuals with family history were at high risk.

Associations between season of birth and age both at menarche and at menopause / 中华流行病学杂志

Objective To examine the associations between season of birth and factors as age at menarche,age at menopause and reproductive span.Methods A total of 285 186 female from the China Kadoorie Biobank,with complete data on critical variables and had menarche at 9-18 years old,were included.A total of 132 373 female with natural menopause were included for the analysis on age at menopause and reproductive span.Multiple linear regression models were used to assess the associations of birth season and the age at menarche,menopause,and reproductive span.Subgroup analyses were performed on birth cohorts and urban/rural residence.Results Compared with the Spring-born (March,April,and May),participants who were born in Summer (June,July,and August),Autumn (September,October,and November),and Winter (December,January,and February)appeared late on both age at menarche and menopause.Multivariable-adjusted coefficients (95％ CI)appeared as 0.14 (95％CI:0.13-0.16),0.26(95％CI:0.24-0.27),0.10 (95％CI:0.08-0.12) for age at menarche respectively and 0.14 (95％CI:0.08-0.20),0.18 (95％CI:0.12-0.24),0.09 (95％CI:0.03-0.16) for age at menopause respectively.No statistically significant association was found between the season of birth and reproductive span.The association was consistent between urban and rural residents and across the birth cohorts.Conclusions female born in spring showed both earlier age on both menarche and menopause,compared to the ones born in other seasons.Our findings suggested that exposures in early life with some degree of seasonal variation might influence the development of female reproductive system.

Associations between season of birth and age both at menarche and at menopause / 中华流行病学杂志

Objective To examine the associations between season of birth and factors as age at menarche,age at menopause and reproductive span.Methods A total of 285 186 female from the China Kadoorie Biobank,with complete data on critical variables and had menarche at 9-18 years old,were included.A total of 132 373 female with natural menopause were included for the analysis on age at menopause and reproductive span.Multiple linear regression models were used to assess the associations of birth season and the age at menarche,menopause,and reproductive span.Subgroup analyses were performed on birth cohorts and urban/rural residence.Results Compared with the Spring-born (March,April,and May),participants who were born in Summer (June,July,and August),Autumn (September,October,and November),and Winter (December,January,and February)appeared late on both age at menarche and menopause.Multivariable-adjusted coefficients (95％ CI)appeared as 0.14 (95％CI:0.13-0.16),0.26(95％CI:0.24-0.27),0.10 (95％CI:0.08-0.12) for age at menarche respectively and 0.14 (95％CI:0.08-0.20),0.18 (95％CI:0.12-0.24),0.09 (95％CI:0.03-0.16) for age at menopause respectively.No statistically significant association was found between the season of birth and reproductive span.The association was consistent between urban and rural residents and across the birth cohorts.Conclusions female born in spring showed both earlier age on both menarche and menopause,compared to the ones born in other seasons.Our findings suggested that exposures in early life with some degree of seasonal variation might influence the development of female reproductive system.

A review of pension status quo in China and domestic and overseas pension models / 中华流行病学杂志

With the aging of population and progressive decline of traditional pension model,the problems in the aged supporting have caused serious social concern in China.Since 1980's,different opinions about pension models have been suggested in many research papers.This paper summarizes the characteristics of different pension model used in both China and abroad in terms of the financial sources of the aged supporting,life style and the combination with medical service,suggesting to establish a pension model with Chinese characteristics to provide multiple and personalized services on the basis of China's national situation and successful experiences of other countries.

A review of pension status quo in China and domestic and overseas pension models / 中华流行病学杂志

With the aging of population and progressive decline of traditional pension model,the problems in the aged supporting have caused serious social concern in China.Since 1980's,different opinions about pension models have been suggested in many research papers.This paper summarizes the characteristics of different pension model used in both China and abroad in terms of the financial sources of the aged supporting,life style and the combination with medical service,suggesting to establish a pension model with Chinese characteristics to provide multiple and personalized services on the basis of China's national situation and successful experiences of other countries.