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1. Comparative studies of 2168 plasma proteins measured by two affinity-based platforms in 4000 Chinese adults

Author

Baihan Wang, Alfred Pozarickij, Mohsen Mazidi, Neil Wright, Pang Yao, Saredo Said, Andri Iona, Christiana Kartsonaki, Hannah Fry, Kuang Lin, Yiping Chen, Huaidong Du, Daniel Avery, Dan Schmidt-Valle, Canqing Yu, Dianjianyi Sun, Jun Lv, Michael Hill, Liming Li, Derrick A. Bennett, Rory Collins, Robin G. Walters, Robert Clarke, Iona Y. Millwood, Zhengming Chen, and On behalf of China Kadoorie Biobank Collaborative Group

Subjects
Science
Abstract

Abstract Proteomics offers unique insights into human biology and drug development, but few studies have directly compared the utility of different proteomics platforms. We measured plasma levels of 2168 proteins in 3976 Chinese adults using both Olink Explore and SomaScan platforms. The correlation of protein levels between platforms was modest (median rho = 0.29), with protein abundance and data quality parameters being key factors influencing correlation. For 1694 proteins with one-to-one matched reagents, 765 Olink and 513 SomaScan proteins had cis-pQTLs, including 400 with colocalising cis-pQTLs. Moreover, 1096 Olink and 1429 SomaScan proteins were associated with BMI, while 279 and 154 proteins were associated with risk of ischaemic heart disease, respectively. Addition of Olink and SomaScan proteins to conventional risk factors for ischaemic heart disease improved C-statistics from 0.845 to 0.862 (NRI: 12.2%) and 0.863 (NRI: 16.4%), respectively. These results demonstrate the utility of these platforms and could inform the design and interpretation of future studies.

Published
2025
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2. Proteo-genomic analyses in relatively lean Chinese adults identify proteins and pathways that affect general and central adiposity levels

Author

Andri Iona, Pang Yao, Alfred Pozarickij, Christiana Kartsonaki, Saredo Said, Neil Wright, Kuang Lin, Iona Millwood, Hannah Fry, Mohsen Mazidi, Baihan Wang, Yiping Chen, Huaidong Du, Ling Yang, Daniel Avery, Dan Schmidt, Dianjianyi Sun, Pei Pei, Jun Lv, Canqing Yu, Michael Hill, Junshi Chen, Fiona Bragg, Derrick Bennett, Robin Walters, Liming Li, Robert Clarke, Zhengming Chen, and China Kadoorie Biobank Collaborative Group

Subjects
Biology (General), QH301-705.5
Abstract

Abstract 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). Genetically-predicted body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-hip ratio (WHR) are significantly (FDR

Published
2024
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3. One-size-fits-all versus risk-category-based screening interval strategies for cardiovascular disease prevention in Chinese adults: a prospective cohort studyResearch in context

Author

Zhijia Sun, Yu Ma, Canqing Yu, Dianjianyi Sun, Yuanjie Pang, Pei Pei, Ling Yang, Yiping Chen, Huaidong Du, Hao Zhang, Xiaoming Yang, Maxim Barnard, Robert Clarke, Junshi Chen, Zhengming Chen, Liming Li, Jun Lv, Rory Collins, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Lazaros Belbasis, Ruth Boxall, Ka Hung Chan, Charlotte Clarke, Johnathan Clarke, Ahmed Edris Mohamed, Hannah Fry, Simon Gilbert, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Hubert Lam, Kuang Lin, James Liu, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Maryanm Rahmati, Paul Ryder, Saredo Said, Dan Schmidt, Becky Stevens, Iain Turnbull, Baihan Wang, Lin Wang, Neil Wright, Pang Yao, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Lang Pan, Zengchang Pang, Ruqin Gao, Shanpeng Li, Haiping Duan, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Wei Sun, Shichun Yan, Xiaoming Cui, Chi Wang, Zhenyuan Wu, Yanjie Li, Quan Kang, Huiming Luo, Tingting Ou, Xiangyang Zheng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su. Fang Liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Mei Lin, Zhenzhen Lu, Lifang Zhou, Changping Xie, Jian Lan, Tingping Zhu, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xiaoyu Chang, Mingqiang Yuan, Xia Wu, Wei Jiang, Jiaqiu Liu, Qiang Sun, Faqing Chen, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Kai Kang, Shixian Feng, Huizi Tian, Lei Fan, XiaoLin Li, Huarong Sun, Pan He, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Xiaoyi Zhang, Yuan Cao, Kaixu Xie, Lingli Chen, Dun Shen, Xiaojun Li, Donghui Jin, Li Yin, Huilin Liu, Zhongxi Fu, Xin Xu, Jianwei Chen, Yuan Peng, Libo Zhang, and Chan Qu

Subjects
Cardiovascular disease, Screening, Primary prevention, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Published
2024
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4. Association between health insurance cost-sharing and choice of hospital tier for cardiovascular diseases in China: a prospective cohort studyResearch in context

Author

Muriel Levy, John Buckell, Robert Clarke, Nina Wu, Pei Pei, Dianjianyi Sun, Daniel Avery, Hua Zhang, Jun Lv, Canqing Yu, Liming Li, Zhengming Chen, Winnie Yip, Yiping Chen, Borislava Mihaylova, Junshi Chen, Rory Collins, Chen Wang, Richard Peto, Robin Walters, Maxim Barnard, Derrick Bennett, Ruth Boxall, Kahung Chan, Johnathan Clarke, Huaidong Du, Ahmed Edris Mohamed, Hannah Fry, Simon Gilbert, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Hubert Lam, Kuang Lin, James Liu, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozaricki, Paul Ryder, Saredo Said, Dan Schmidt, Becky Stevens, Iain Turnbull, Baihan Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Naying Chen, Duo Liu, Zhenzhu Tang, Ningyu Chen, Qilian Jiang, Jian Lan, Mingqiang Li, Yun Liu, Fanwen Meng, Jinhuai Meng, Rong Pan, Yulu Qin, Ping Wang, Sisi Wang, Liuping Wei, Liyuan Zhou, Caixia Dong, Pengfei Ge, Xiaolan Ren, Zhongxiao Li, Enke Mao, Tao Wang, Hui Zhang, Xi Zhang, Jinyan Chen, Ximin Hu, Xiaohuan Wang, Zhendong Guo, Huimei Li, Yilei Li, Min Weng, Shukuan Wu, Shichun Yan, Mingyuan Zou, Xue Zhou, Ziyan Guo, Quan Kang, Yanjie Li, Bo Yu, Qinai Xu, Liang Chang, Lei Fan, Shixian Feng, Ding Zhang, Gang Zhou, Yulian Gao, Tianyou He, Pan He, Chen Hu, Huarong Sun, Xukui Zhang, Biyun Chen, Zhongxi Fu, Yuelong Huang, Huilin Liu, Qiaohua Xu, Li Yin, Huajun Long, Xin Xu, Hao Zhang, Libo Zhang, Jian Su, Ran Tao, Ming Wu, Jie Yang, Jinyi Zhou, Yonglin Zhou, Yihe Hu, Yujie Hua, Jianrong Jin, Fang Liu, Jingchao Liu, Yan Lu, Liangcai Ma, Aiyu Tang, Jun Zhang, Liang Cheng, Ranran Du, Ruqin Gao, Feifei Li, Shanpeng Li, Yongmei Liu, Feng Ning, Zengchang Pang, Xiaohui Sun, Xiaocao Tian, Shaojie Wang, Yaoming Zhai, Wei Hou, Silu Lv, Junzheng Wang, Xiaofang Chen, Xianping Wu, Ningmei Zhang, Xiaoyu Chang, Jianguo Li, Jiaqiu Liu, Guojin Luo, Qiang Sun, Xunfu Zhong, Weiwei Gong, Ruying Hu, Hao Wang, Meng Wang, Min Yu, Lingli Chen, Qijun Gu, Dongxia Pan, Chunmei Wang, Kaixu Xie, Xiaoyi Zhang, Hongyuan Chen, Liyang Liu, Haiyan Gou, Xun Wang, Jing Ding, Ning Zhang, Yueshi Mao, Shanshan Zhou, Lirong Jin, Xin Cheng, Yun Lu, Li Chen, Zilong Hao, Xiaona Xing, Lei Wang, Naixin Ju, Yiting Mao, Shuya Li, Peng Du, Deren Wang, Xiaojia Sun, Shihao You, Weizhi Wang, Yanmei Zhu, Xiaojiu Li, and Yi Dong

Subjects
Hospital type, Cardiovascular diseases, Healthcare seeking behaviour, China, Public aspects of medicine, RA1-1270
Abstract

Summary: 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. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

Published
2024
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5. Causal association between snoring and stroke: a Mendelian randomization study in a Chinese populationResearch in context

Author

Yunqing Zhu, Zhenhuang Zhuang, Jun Lv, Dianjianyi Sun, Pei Pei, Ling Yang, Iona Y. Millwood, Robin G. Walters, Yiping Chen, Huaidong Du, Xianping Wu, Dan Schmidt, Daniel Avery, Junshi Chen, Zhengming Chen, Liming Li, Canqing Yu, Robert Clarke, Rory Collins, Yu Guo, Richard Peto, Robin Walter, Derrick Bennett, Ruth Boxall, Sue Burgess, Ka Hung Chan, Yumei Chang, Johnathan Clarke, Ahmed Edris Mohamed, Zammy Fairhurst-Hunter, Hannah Fry, Mike Hill, Michael Holmes, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Rene Kerosi, Kuang Lin, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Paul Ryder, Saredo Said, Paul Sherliker, Becky Stevens, Iain Turnbull, Robin Walters, Lin Wang, Neil Wright, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Chao Liu, Qingmei Xia, Zengchang Pang, Ruqin Gao, Shanpeng Li, Haiping Duan, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Wei Sun, Shichun Yan, Xiaoming Cui, Chi Wang, Zhenyuan Wu, Yanjie Li, Quan Kang, Huiming Luo, Tingting Ou, Xiangyang Zheng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su, Fang Liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Mei Lin, Zhenzhen Lu, Lifang Zhou, Changping Xie, Jian Lan, Tingping Zhu, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Yulu Qin, Sisi Wang, Ningmei Zhang, Xiaofang Chen, Xiaoyu Chang, Mingqiang Yuan, Xia Wu, Wei Jiang, Jiaqiu Liu, Qiang Sun, Faqing Chen, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi zhang, Kai Kang, Shixian Feng, Huizi Tian, Lei Fan, XiaoLin Li, Huarong Sun, Pan He, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Xiaoyi Zhang, Yuan Cao, Kaixu Xie, Lingli Chen, Dun Shen, Xiaojun Li, Donghui Jin, Li Yin, Huilin Liu, Zhongxi Fu, Xin Xu, Hao Zhang, Jianwei Chen, Yuan Peng, Libo Zhang, and Chan Qu

Subjects
Snoring, Stroke, Body mass index, Mendelian randomization, Public aspects of medicine, RA1-1270
Abstract

Summary: 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. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

Published
2024
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6. Pleiotropic genetic architecture and novel loci for C-reactive protein levels

Author

Fotios Koskeridis, Evangelos Evangelou, Saredo Said, Joseph J. Boyle, Paul Elliott, Abbas Dehghan, and Ioanna Tzoulaki

Subjects
Science
Abstract

Chronic inflammation and lipometabolism share many causal genes and possibly pathways. Here, the authors use a multi-trait GWAS approach to study shared genetic determinants of low-grade inflammation, measured by C-reactive protein (CRP), and closely linked lipid and metabolic pathways.

Published
2022
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7. Genetic analysis of over half a million people characterises C-reactive protein loci

Author

Saredo Said, Raha Pazoki, Ville Karhunen, Urmo Võsa, Symen Ligthart, Barbara Bodinier, Fotios Koskeridis, Paul Welsh, Behrooz Z. Alizadeh, Daniel I. Chasman, Naveed Sattar, Marc Chadeau-Hyam, Evangelos Evangelou, Marjo-Riitta Jarvelin, Paul Elliott, Ioanna Tzoulaki, and Abbas Dehghan

Subjects
Science
Abstract

Inflammation is associated with a variety of diseases. Here, the authors identify 266 genetic loci associated with C-reactive protein levels, a marker of inflammation, in >500,000 Europeans, along with associated pathways, clinical outcomes and potential causal associations with disease.

Published
2022
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8. Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes

Author

Raha Pazoki, Marijana Vujkovic, Joshua Elliott, Evangelos Evangelou, Dipender Gill, Mohsen Ghanbari, Peter J. van der Most, Rui Climaco Pinto, Matthias Wielscher, Matthias Farlik, Verena Zuber, Robert J. de Knegt, Harold Snieder, André G. Uitterlinden, Lifelines Cohort Study, Julie A. Lynch, Xiyun Jiang, Saredo Said, David E. Kaplan, Kyung Min Lee, Marina Serper, Rotonya M. Carr, Philip S. Tsao, Stephen R. Atkinson, Abbas Dehghan, Ioanna Tzoulaki, M. Arfan Ikram, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Behrooz Z. Alizadeh, Christopher J. O’Donnell, Danish Saleheen, Benjamin F. Voight, Kyong-Mi Chang, Mark R. Thursz, Paul Elliott, and the VA Million Veteran Program

Subjects
Science
Abstract

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.

Published
2021
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10. Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese

Author

Yu Guo, Derrick Bennett, Huaidong Du, Liming Li, Robert Clarke, Zhengming Chen, Junshi Chen, Ruying Hu, Kaixu Xie, Min Yu, Qiang Sun, Jun Zhang, Ling Yang, Shuo Zhang, Dianjianyi Sun, Hao Wang, Hua Zhang, Lingli Chen, Hao Zhang, Liang Cheng, Chao Liu, Hui Zhang, Fang Liu, Xin Xu, Wei Jiang, Tao Wang, Rory Collins, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Ruth Boxall, Yumei Chang, Yiping Chen, Simon Gilbert, Alex Hacker, Michael Holmes, Christiana Kartsonaki, Rene Kerosi, Kuang Lin, Iona Millwood, Qunhua Nie, Paul Ryder, Sam Sansome, Dan Schmidt, Rajani Sohoni, Becky Stevens, Iain Turnbull, Lin Wang, Neil Wright, Xiaoming Yang, Xiao Han, Can Hou, Pei Pei, Canqing Yu, Zengchang Pang, Ruqin Gao, Shanpeng Li, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Xiaocao Tian, Yaoming Zhai, Feng Ning, Xiaohui Sun, Silu Lv, Junzheng Wang, Yanjie Li, Quan Kang, Zhendong Guo, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Jianrong Jin, Liuping Wei, Liyuan Zhou, Yulu Qin, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Jiaqiu Liu, Xiaolan Ren, Enke Mao, Xiaoping Wang, Shixian Feng, Huarong Sun, Pan He, Xukui Zhang, Zhongxi Fu, Libo Zhang, Jingchao Liu, Andri Iona, Paul Sherliker, Wei Hou, Xiangyang Zheng, Yilei Li, Huimei Li, Yun Liu, Ningyu Chen, Caixia Dong, Xi Zhang, Lei Fan, Donghui Jin, Wei Sun, Jian Su, Mike Hill, Feifei Li, Shukuan Wu, Jian Lan, Sisi Wang, Kai Kang, Xiao Li, Pang Yao, Songchun Yang, Shichun Yan, Huilin Liu Li Yin, Chi Wang, Ka Hung Chan, Lifang Zhou, Xiaoyu Chang, Mohsen Mazidi, Mei Lin, Yuanjie Pang, Iona Y Millwood, Xiaoming Cui, Yuan Cao, Xia Wu, Pek Kei Im, Xiaoyi Zhang, Dong Sun, Robin G Walters, Zhijia Sun, Sushila Burgess, Sue Burgess, Johnathan Clarke, Ahmed Edris Mohamed, Zammy Fairhurst-Hunter, Hannah Fry, Maria Kakkoura, Sam Morris, Alfred Pozarickij, Saredo Said, Qingmei Xia, Haiping Duan, Zhenyuan Wu, Huiming Luo, Tingting Ou, Zhenzhen Lu, Changping Xie, Tingping Zhu, Mingqiang Yuan, Faqing Chen, Huizi Tian, Dun Shen, Xiaojun Li, Jianwei Chen, Yuan Peng, and Chan Qu

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

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). Four previously developed PRSs were included, and new PRSs for stroke and its subtypes were developed. The PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing set. Cox proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes (ischaemic stroke (IS), intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH)).Results In the testing set, during 872 919 person-years of follow-up, 8514 incident stroke events were documented. The PRSs of any stroke (AS) and IS were both positively associated with risks of AS, IS and ICH (p

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11. Long-Term Exposure to Fine Particulate Matter and Incidence of Esophageal Cancer: A Prospective Study of 0.5 Million Chinese Adults

Author

Dong Sun, Cong Liu, Yunqing Zhu, Canqing Yu, Yu Guo, Dianjianyi Sun, Yuanjie Pang, Pei Pei, Huaidong Du, Ling Yang, Yiping Chen, Xia Meng, Yang Liu, Jun Zhang, Dan Schmidt, Daniel Avery, Junshi Chen, Zhengming Chen, Jun Lv, Haidong Kan, Liming Li, Robert Clarke, Rory Collins, Richard Peto, Robin Walters, Derrick Bennett, Ruth Boxall, Sue Burgess, Ka Hung Chan, Yumei Chang, Johnathan Clarke, Ahmed Edris Mohamed, Zammy Fairhurst-Hunter, Hannah Fry, Simon Gilbert, Alex Hacker, Mike Hill, Michael Holmes, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Rene Kerosi, Kuang Lin, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Paul Ryder, Saredo Said, Sam Sansome, Paul Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Lin Wang, Neil Wright, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Chao Liu, Qingmei Xia, Zengchang Pang, Ruqin Gao, Shanpeng Li, Haiping Duan, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Wei Sun, Shichun Yan, Xiaoming Cui, Chi Wang, Zhenyuan Wu, Yanjie Li, Quan Kang, Huiming Luo, Tingting Ou, Xiangyang Zheng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su, Fang Liu, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Mei Lin, Zhenzhen Lu, Lifang Zhou, Changping Xie, Jian Lan, Tingping Zhu, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xiaoyu Chang, Mingqiang Yuan, Xia Wu, Wei Jiang, Jiaqiu Liu, Qiang Sun, Faqing Chen, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Kai Kang, Shixian Feng, Huizi Tian, Lei Fan, XiaoLin Li, Huarong Sun, Pan He, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Xiaoyi Zhang, Yuan Cao, Kaixu Xie, Lingli Chen, Dun Shen, Xiaojun Li, Donghui Jin, Li Yin, Huilin Liu, Zhongxi Fu, Xin Xu, Hao Zhang, Jianwei Chen, Yuan Peng, Libo Zhang, and Chan Qu

Subjects
Hepatology, Gastroenterology
Published
2023
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12. Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes

Author

Stephen R. Atkinson, Philip S. Tsao, Evangelos Evangelou, VA Million Veteran Program, Karl-Heinz Herzig, David E. Kaplan, Marina Serper, Behrooz Z. Alizadeh, Benjamin F. Voight, Xiyun Jiang, Julie A. Lynch, Dipender Gill, Danish Saleheen, Marjo-Riitta Järvelin, André G. Uitterlinden, Rui Pinto, Raha Pazoki, Peter J. van der Most, Paul Elliott, Verena Zuber, Matthias Farlik, Ioanna Tzoulaki, Mark Thursz, Harold Snieder, Marijana Vujkovic, Christopher J. O'Donnell, Mohsen Ghanbari, Kyung Min Lee, Saredo Said, Matthias Wielscher, Kyong-Mi Chang, M. Arfan Ikram, Joshua Elliott, Rotonya M. Carr, Robert J. de Knegt, Abbas Dehghan, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Medical Research Council (MRC), Epidemiology, Gastroenterology & Hepatology, and Internal Medicine

Subjects
Enzymologic, Male, 0301 basic medicine, LD SCORE REGRESSION, General Physics and Astronomy, Physiology, Genome-wide association study, Cardiovascular, Oral and gastrointestinal, DISEASE, Cohort Studies, Rotterdam Study, 0302 clinical medicine, Risk Factors, Databases, Genetic, 2.1 Biological and endogenous factors, Aetiology, POPULATION, RISK, education.field_of_study, Multidisciplinary, biology, medicine.diagnostic_test, HERITABILITY, Liver Disease, Alanine Transaminase, gamma-Glutamyltransferase, Single Nucleotide, Middle Aged, Heart Disease, Liver, Cardiovascular Diseases, VA Million Veteran Program, MENDELIAN RANDOMIZATION, Female, 030211 gastroenterology & hepatology, HEALTH, Science, Population, Single-nucleotide polymorphism, BIOBANK, Polymorphism, Single Nucleotide, Gene Expression Regulation, Enzymologic, White People, General Biochemistry, Genetics and Molecular Biology, Databases, 03 medical and health sciences, Insulin resistance, Metabolic Diseases, Genetic, Lifelines Cohort Study, SDG 3 - Good Health and Well-being, Mendelian randomization, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Polymorphism, GENOME-WIDE ASSOCIATION, education, Metabolic and endocrine, METAANALYSIS, Aged, Genetic testing, business.industry, General Chemistry, Mendelian Randomization Analysis, Alkaline Phosphatase, Lipid Metabolism, medicine.disease, Good Health and Well Being, 030104 developmental biology, Gene Expression Regulation, Alanine transaminase, biology.protein, Insulin Resistance, Digestive Diseases, business, Genome-Wide Association Study
Abstract

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.

Published
2021

13. Tobacco smoking and risks of more than 470 diseases in China: a prospective cohort study

Author

Ka Hung Chan, Neil Wright, Dan Xiao, Yu Guo, Yiping Chen, Huaidong Du, Ling Yang, Iona Y Millwood, Pei Pei, Junzheng Wang, Iain Turnbull, Simon Gilbert, Daniel Avery, Christiana Kartsonaki, Canqing Yu, Junshi Chen, Jun Lv, Robert Clarke, Rory Collins, Richard Peto, Liming Li, Chen Wang, Zhengming Chen, Derrick Bennett, Ruth Boxall, Sushila Burgess, Peter Ka Hung Chan, Johnathan Clarke, Ahmed Edris Mohamed, Hannah Fry, Mike Hill, Becky Pek Kei Im, Andri Iona, Maria Kakkoura, Hubert Lam, Kuang Lin, Mohsen Mazidi, Sam Morris, Qunhua Nie, Alfred Pozarickij, Paul Ryder, Saredo Said, Dan Schmidt, Paul Sherliker, Rebecca Stevens, Robin Walters, Lin Wang, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Naying Chen, Duo Liu, Zhenzhu Tang, Ningyu Chen, Qilian Jiang, Jian Lan, Mingqiang Li, Yun Liu, Fanwen Meng, Jinhuai Meng, Rong Pan, Yulu Qin, Ping Wang, Sisi Wang, Liuping Wei, Liyuan Zhou, Caixia Dong, Pengfei Ge, Xiaolan Ren, Zhongxiao Li, Enke Mao, Tao Wang, Hui Zhang, Xi Zhang, Jinyan Chen, Ximin Hu, Xiaohuan Wang, Zhendong Guo, Huimei Li, Yilei Li, Min Weng, Shukuan Wu, Shichun Yan, Mingyuan Zou, Xue Zhou, Ziyan Guo, Quan Kang, Yanjie Li, Bo Yu, Qinai Xu, Liang Chang, Lei Fan, Shixian Feng, Ding Zhang, Gang Zhou, Yulian Gao, Tianyou He, Pan He, Chen Hu, Huarong Sun, Xukui Zhang, Biyun Chen, Zhongxi Fu, Yuelong Huang, Huilin Liu, Qiaohua Xu, Li Yin, Huajun Long, Xin Xu, Hao Zhang, Libo Zhang, Jian Su, Ran Tao, Ming Wu, Jie Yang, Jinyi Zhou, Yonglin Zhou, Yihe Hu, Yujie Hua, Jianrong Jin, Fang Liu, Jingchao Liu, Yan Lu, Liangcai Ma, Aiyu Tang, Jun Zhang, Liang Cheng, Ranran Du, Ruqin Gao, Feifei Li, Shanpeng Li, Yongmei Liu, Feng Ning, Zengchang Pang, Xiaohui Sun, Xiaocao Tian, Shaojie Wang, Yaoming Zhai, Hua Zhang, Wei Hou, Silu Lv, Xiaofang Chen, Xianping Wu, Ningmei Zhang, Weiwei Zhou, Jianguo Li, Jiaqiu Liu, Guojin Luo, Qiang Sun, Xunfu Zhong, Weiwei Gong, Ruying Hu, Hao Wang, Meng Wang, Min Yu, Lingli Chen, Qijun Gu, Dongxia Pan, Chunmei Wang, Kaixu Xie, Xiaoyi Zhang, and group, China Kadoorie Biobank collaborative

Subjects
Adult, Male, Aged, 80 and over, China, Cost of Illness, Smoking, Public Health, Environmental and Occupational Health, Tobacco Smoking, Humans, Female, Prospective Studies, Middle Aged, Aged
Abstract

Background Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China. Methods We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30–79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100–150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10–12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35–84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing. Findings At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35–84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08–1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42–1·58] vs 1·25 [1·20–1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89–2·24) for overall mortality and 1·32 (1·27–1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking. Interpretation Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention. Funding British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.

Published
2022

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