Risk prediction of ischemic heart disease using plasma proteomics, conventional risk factors and polygenic scores in Chinese and European adults.

Plasma proteomics could enhance risk prediction for multiple diseases beyond conventional risk factors or polygenic scores (PS). To assess utility of proteomics for risk prediction of ischemic heart disease (IHD) compared with conventional risk factors and PS in Chinese and European populations. A nested case-cohort study measured plasma levels of 2923 proteins using Olink Explore panel in ~ 4000 Chinese adults (1976 incident IHD cases and 2001 sub-cohort controls).

Proteo-genomic analyses in relatively lean Chinese adults identify proteins and pathways that affect general and central adiposity levels.

Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²).

Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited.

Background: Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels.

Methods: The prospective China Kadoorie Biobank recruited >512 000 adults aged 30-79 years in 2004-08 and genotyped a random subset of 76 000 participants.

DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

Background: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty.

The Role of Active and Passive Smoking in Chronic Obstructive Pulmonary Disease and Systemic Inflammation: A 12-year Prospective Study in China.

Background: There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions.

Methods: The China Kadoorie Biobank cohort was followed up from the 2004-08 baseline survey to 31 December 2018.

Dietary factors and patterns in relation to risk of later-onset ulcerative colitis in Chinese: A prospective study of 0.5 million people.

Background: There is limited evidence on the associations of dietary factors and patterns with risk of later-onset ulcerative colitis (UC) in Chinese adults.

Aims: To investigate the associations of dietary factors and patterns with risk of later-onset UC in Chinese.

Methods: The prospective China Kadoorie Biobank cohort study recruited 512,726 participants aged 30-79.

Predictive value of 8-year blood pressure measures in intracerebral haemorrhage risk over 5 years.

Aims: The relationships between long-term blood pressure (BP) measures and intracerebral haemorrhage (ICH), as well as their predictive ability on ICH, are unclear. In this study, we aim to investigate the independent associations of multiple BP measures with subsequent 5-year ICH risk, as well as the incremental value of these measures over a single-point BP measurement in ICH risk prediction.

Methods And Results: We included 12 398 participants from the China Kadoorie Biobank (CKB) who completed three surveys every 4-5 years.

Proteomic Analyses in Diverse Populations Improved Risk Prediction and Identified New Drug Targets for Type 2 Diabetes.

Objective: Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D).

Research Design And Methods: We measured plasma levels of 2,923 proteins using Olink Explore among ∼2,000 randomly selected participants from China Kadoorie Biobank (CKB) without prior diabetes at baseline. Cox regression assessed associations of individual protein with incident T2D (n = 92 cases).

Reproductive factors and risk of lung cancer among 300,000 Chinese female never-smokers: evidence from the China Kadoorie Biobank study.

Background: Lung cancer is the leading cause of cancer mortality among Chinese females despite the low smoking prevalence among this population. This study assessed the roles of reproductive factors in lung cancer development among Chinese female never-smokers.

Methods: The prospective China Kadoorie Biobank (CKB) recruited over 0.

Association between health insurance cost-sharing and choice of hospital tier for cardiovascular diseases in China: a prospective cohort study.

Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers.

A wide landscape of morbidity and mortality risk associated with marital status in 0.5 million Chinese men and women: a prospective cohort study.

Background: A comprehensive depiction of long-term health impacts of marital status is lacking.

Methods: Sex-stratified phenome-wide association analyses (PheWAS) of marital status (living with vs. without a spouse) were performed using baseline (2004-2008) and follow-up information (ICD10-coded events till Dec 31, 2017) from the China Kadoorie Biobank (CKB).

Causal association between snoring and stroke: a Mendelian randomization study in a Chinese population.

Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke.

Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke.

Alcohol intake and cause-specific mortality: conventional and genetic evidence in a prospective cohort study of 512 000 adults in China.

Background: Genetic variants that affect alcohol use in East Asian populations could help assess the causal effects of alcohol consumption on cause-specific mortality. We aimed to investigate the associations between alcohol intake and cause-specific mortality using conventional and genetic epidemiological methods among more than 512 000 adults in China.

Methods: The prospective China Kadoorie Biobank cohort study enrolled 512 724 adults (210 205 men and 302 519 women) aged 30-79 years, during 2004-08.

Plasma Proteomics to Identify Drug Targets for Ischemic Heart Disease.

Background: 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.

Objectives: The purpose of this study was to examine associations of proteomics and genetics data with IHD in population studies to discover novel preventive treatments.

Methods: 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.

Genetic influences on alcohol flushing in East Asian populations.

Background: Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.

Methods: We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake.

Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults.

Adiposity is associated with multiple diseases and traits, but little is known about the causal relevance and mechanisms underlying these associations. Large-scale proteomic profiling, especially when integrated with genetic data, can clarify mechanisms linking adiposity with disease outcomes. We examined the associations of adiposity with plasma levels of 1463 proteins in 3977 Chinese adults, using measured and genetically-instrumented BMI.

Genome-wide polygenic risk score, cardiometabolic risk factors, and type 2 diabetes mellitus in the Chinese population.

Objective: Type 2 diabetes (T2D) is caused by both genetic and cardiometabolic risk factors. However, the magnitude of the genetic predisposition of T2D in the Chinese population remains largely unknown.

Methods: This study included 93,488 participants from the China Kadoorie Biobank, and multiple polygenic risk scores (PRS) were calculated.

Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese.

Background And Purpose: Previous studies, mostly focusing on the European population, have reported polygenic risk scores (PRSs) might achieve risk stratification of stroke. We aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese population.

Methods: Participants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set (n=22 191) and a population-based testing set (n=72 150).

Genotyping and population characteristics of the China Kadoorie Biobank.

The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history.