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Purpose: Different populations may exhibit differences in dietary intakes, which may result in heterogeneities in diet–disease associations. We compared intakes of major food groups overall, by sex, and by socio-economic status (SES) (defined as both education and income), between participants in the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). Methods: Data were from ~ 25,000 CKB participants who completed a validated interviewer-administered computer-based questionnaire (2013–2014) and ~ 74,000 UKB participants who completed ≥ 3 web-based 24-h dietary assessments (2009–2012). Intakes of 12 major food groups and five beverages were harmonized and compared between the cohorts overall, by sex and by SES. Multivariable-adjusted linear regression examined the associations between dietary intakes and body mass index (BMI) in each cohort. Results: CKB participants reported consuming more rice, eggs, vegetables, soya products, and less wheat, other staple foods (other than rice and wheat), fish, poultry, all dairy products, fruit, and beverages compared to UKB participants. Red meat intake was similar in both cohorts. Having a higher SES was generally associated with a higher consumption of foods and beverages in CKB, whereas in UKB dietary intakes differed more by education and income, with a positive association observed for meat and income in both UKB and CKB but an inverse association observed for education in UKB. Associations of dietary intakes with BMI varied between the two cohorts. Conclusion: The large differences in dietary intakes and their associations with SES and BMI could provide insight into the interpretation of potentially different diet–disease associations between CKB and UKB. [ABSTRACT FROM AUTHOR]

Background: Both genetic and cardiovascular factors contribute to the risk of developing heart failure (HF), but whether idea cardiovascular health metrics (ICVHMs) offset the genetic association with incident HF remains unclear.Objectives: To investigate the genetic association with incident HF as well as the modification effect of ICVHMs on such genetic association in Chinese and British populations.Methods: An ICVHMs based on smoking, drinking, physical activity, diets, body mass index, waist circumference, blood pressure, blood glucose, and blood lipids, and a polygenic risk score (PRS) for HF were constructed in the China Kadoorie Biobank (CKB) of 96,014 participants and UK Biobank (UKB) of 335,782 participants which were free from HF and severe chronic diseases at baseline.Results: During the median follow-up of 11.38 and 8.73 years, 1451 and 3169 incident HF events were documented in CKB and UKB, respectively. HF risk increased monotonically with the increase of PRS per standard deviation (CKB: hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07, 1.32; UKB: 1.07; 1.03, 1.11; P for trend < 0.001). Each point increase in ICVHMs was associated with 15% and 20% lower risk of incident HF in CKB (0.85; 0.81, 0.90) and UKB (0.80; 0.77, 0.82), respectively. Compared with unfavorable ICVHMs, favorable ICVHMs was associated with a lower HF risk, with 0.71 (0.44, 1.15), 0.41 (0.22, 0.77), and 0.48 (0.30, 0.77) in the low, intermediate, and high genetic risk in CKB and 0.34 (0.26, 0.44), 0.32 (0.25, 0.41), and 0.37 (0.28, 0.47) in UKB (P for multiplicative interaction > 0.05). Participants with low genetic risk and favorable ICVHMs, as compared with high genetic risk and unfavorable ICVHMs, had 56~72% lower risk of HF (CKB 0.44; 0.28, 0.70; UKB 0.28; 0.22, 0.37). No additive interaction between PRS and ICVHMs was observed (relative excess risk due to interaction was 0.05 [-0.22, 0.33] in CKB and 0.04 [-0.14, 0.22] in UKB).Conclusions: In CKB and UKB, genetic risk and ICVHMs were independently associated with the risk of incident HF, which suggested that adherence to favorable cardiovascular health status was associated with a lower HF risk among participants with all gradients of genetic risk. [ABSTRACT FROM AUTHOR]

Background Resting heart rate (RHR) has been associated with risks of mortality and multiple chronic diseases. Previous studies, predominantly conducted in Europeans, have reported 91 independent variants associated with RHR and its genetic correlations with several cardiometabolic traits. Studies from East Asians are lacking. Methods We performed a GWAS for RHR in 87,701 participants aged 30-79 years from China Kadoorie Biobank (CKB). A linear mixed model was used under an additive model. Replication was conducted in 37,251 Chinese participants from CKB and UK Biobank. We conducted LD score regression to quantify genetic correlations across RHR and 11 cardiometabolic traits. Results Only 50 previously reported variants were replicated in CKB (=0.025). We identified ten novel loci associated with RHR (P <5 × 10-8), of which 50 candidate genes were prioritized. RHR showed significant genetic correlations with diastolic blood pressure (rg=0.258, P =5.71 × 10−10), mean arterial pressure (rg=0.225, P =3.08 × 10−8), systolic blood pressure (rg=0.170, P =4.92 × 10−5), plasma glucose (rg=0.197, P =0.003), total cholesterol (rg=0.287, P =0.012), and high-density lipoprotein (rg=0.246, P =0.030). Conclusions We identified ten novel loci associated with RHR in a large Asian cohort. The identified genetic correlations of RHR with blood pressure, glucose, and lipids indicate previously reported association of RHR with risk of all-cause death might be mediated via its correlations with cardiometabolic traits. Key messages Ten novel loci associated with RHR were identified in the Chinese population. RHR showed significant genetic correlations with blood pressure, glucose and lipids. [ABSTRACT FROM AUTHOR]

Integrated analyses of plasma proteomic and genetic markers in prospective studies can clarify the causal relevance of proteins and discover novel targets for ischemic heart disease (IHD) and other diseases. The purpose of this study was to examine associations of proteomics and genetics data with IHD in population studies to discover novel preventive treatments. We conducted a nested case-cohort study in the China Kadoorie Biobank (CKB) involving 1,971 incident IHD cases and 2,001 subcohort participants who were genotyped and free of prior cardiovascular disease. We measured 1,463 proteins in the stored baseline samples using the OLINK EXPLORE panel. Cox regression yielded adjusted HRs for IHD associated with individual proteins after accounting for multiple testing. Moreover, cis -protein quantitative loci (pQTLs) identified for proteins in genome-wide association studies of CKB and of UK Biobank were used as instrumental variables in separate 2-sample Mendelian randomization (MR) studies involving global CARDIOGRAM+C4D consortium (210,842 IHD cases and 1,378,170 controls). Overall 361 proteins were significantly associated at false discovery rate <0.05 with risk of IHD (349 positively, 12 inversely) in CKB, including N-terminal prohormone of brain natriuretic peptide and proprotein convertase subtilisin/kexin type 9. Of these 361 proteins, 212 had cis -pQTLs in CKB, and MR analyses of 198 variants in CARDIOGRAM+C4D identified 13 proteins that showed potentially causal associations with IHD. Independent MR analyses of 307 cis -pQTLs identified in Europeans replicated associations for 4 proteins (FURIN, proteinase-activated receptor-1, Asialoglycoprotein receptor-1, and matrix metalloproteinase-3). Further downstream analyses showed that FURIN, which is highly expressed in endothelial cells, is a potential novel target and matrix metalloproteinase-3 a potential repurposing target for IHD. Integrated analyses of proteomic and genetic data in Chinese and European adults provided causal support for FURIN and multiple other proteins as potential novel drug targets for treatment of IHD. [Display omitted] [ABSTRACT FROM AUTHOR]