1,013 results on '"Zhengming Chen"'
Search Results
2. Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: a cross-sectional analysis across 11 prospective studies
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Yashvee Dunneram, Jia Yi Lee, Cody Z. Watling, Gary E. Fraser, Fayth Miles, Dorairaj Prabhakaran, Krithiga Shridhar, Dimple Kondal, Viswanathan Mohan, Mohammed K. Ali, Kabayam M. Venkat Narayan, Nikhil Tandon, Tammy Y. N. Tong, Tina H. T. Chiu, Ming-Nan Lin, Chin-Lon Lin, Hsin-Chou Yang, Yu-Jen Liang, Darren C. Greenwood, Huaidong Du, Zhengming Chen, Canqing Yu, Maria G. Kakkoura, Gillian K. Reeves, Keren Papier, Sarah Floud, Rashmi Sinha, Linda M. Liao, Erikka Loftfield, Janet E. Cade, Timothy J. Key, and Aurora Perez-Cornago
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Vegetarians ,Vegans ,Meat eaters ,Poultry eaters ,Pescatarians ,Consortium ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies. Methods We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics. Results 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China. Conclusions Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.
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- 2024
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3. Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults
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Alfred Pozarickij, Wei Gan, Kuang Lin, Robert Clarke, Zammy Fairhurst-Hunter, Masaru Koido, Masahiro Kanai, Yukinori Okada, Yoichiro Kamatani, Derrick Bennett, Huaidong Du, Yiping Chen, Ling Yang, Daniel Avery, Yu Guo, Min Yu, Canqing Yu, Dan Schmidt Valle, Jun Lv, Junshi Chen, Richard Peto, Rory Collins, Liming Li, Zhengming Chen, Iona Y. Millwood, Robin G. Walters, and China Kadoorie Biobank Collaborative Group
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Science - Abstract
Abstract Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk.
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- 2024
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4. HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy
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Guinevere Q. Lee, Pragya Khadka, Sarah N. Gowanlock, Dennis C. Copertino, Maggie C. Duncan, F. Harrison Omondi, Natalie N. Kinloch, Jingo Kasule, Taddeo Kityamuweesi, Paul Buule, Samiri Jamiru, Stephen Tomusange, Aggrey Anok, Zhengming Chen, R. Brad Jones, Ronald M. Galiwango, Steven J. Reynolds, Thomas C. Quinn, Zabrina L. Brumme, Andrew D. Redd, and Jessica L. Prodger
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Science - Abstract
Abstract The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest.
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- 2024
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5. One-size-fits-all versus risk-category-based screening interval strategies for cardiovascular disease prevention in Chinese adults: a prospective cohort studyResearch in context
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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
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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).
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- 2024
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6. Reproductive factors and risk of lung cancer among 300,000 Chinese female never-smokers: evidence from the China Kadoorie Biobank study
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Marwa M. A. Elbasheer, Bastian Bohrmann, Yiping Chen, Jun Lv, Dianjianyi Sun, Xia Wu, Xiaoming Yang, Daniel Avery, Liming Li, Zhengming Chen, Christiana Kartsonaki, Ka Hung Chan, and Ling Yang
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Reproductive factors ,Never-smokers ,Lung cancer ,Chinese females ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract 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 0.5 million Chinese adults (0.3 million females) from 10 geographical areas in China in 2004–2008 when information on socio-demographic/lifestyle/environmental factors, physical measurements, medical history, and reproductive history collected through interviewer-administered questionnaires. Cox proportional hazard regression was used to estimate adjusted hazard ratios (HRs) of lung cancer by reproductive factors. Subgroup analyses by menopausal status, birth year, and geographical region were performed. Results During a median follow-up of 11 years, 2,284 incident lung cancers occurred among 282,558 female never-smokers. Ever oral contraceptive use was associated with a higher risk of lung cancer (HR = 1.16, 95% CI: 1.02–1.33) with a significant increasing trend associated with longer duration of use (p-trend = 0.03). Longer average breastfeeding duration per child was associated with a decreased risk (0.86, 0.78–0.95) for > 12 months compared with those who breastfed for 7–12 months. No statistically significant association was detected between other reproductive factors and lung cancer risk. Conclusion Oral contraceptive use was associated with an increased risk of lung cancer in Chinese female never-smokers. Further studies are needed to assess lung cancer risk related to different types of oral contraceptives in similar populations.
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- 2024
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7. Association of physical activity with risk of chronic kidney disease in China: A population-based cohort study
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Kexiang Shi, Yunqing Zhu, Jun Lv, Dianjianyi Sun, Pei Pei, Huaidong Du, Yiping Chen, Ling Yang, Bing Han, Rebecca Stevens, Junshi Chen, Zhengming Chen, Liming Li, and Canqing Yu
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Chronic kidney disease ,Domain ,Intensity ,Physical activity ,Sports ,GV557-1198.995 ,Sports medicine ,RC1200-1245 - Abstract
Background: Information on the association between physical activity (PA) and the risk of chronic kidney disease (CKD) is limited. We aimed to explore the associations of total, domain-specific, and intensity-specific PA with CKD and its subtypes in China. Methods: The study included 475,376 adults from the China Kadoorie Biobank aged 30–79 years during 2004–2008 at baseline. An interviewer-administered questionnaire was used to collect the information about PA, which was quantified as metabolic equivalent of task hours per day (MET-h/day) and categorized into 4 groups based on quartiles. Cox regression was used to analyze the association between PA and CKD risk. Results: During a median follow-up of 12.1 years, 5415 incident CKD cases were documented, including 1159 incident diabetic kidney disease (DKD) cases and 362 incident hypertensive nephropathy (HTN) cases. Total PA was inversely associated with CKD risk, with an adjusted hazard ratio (HR, 95% confidence interval (95%CI)) of 0.83 (0.75–0.92) for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile. Similar results were observed for risk of DKD and HTN, and the corresponding HRs (95%CIs) were 0.75 (0.58–0.97) for DKD risk and 0.56 (0.37–0.85) for HTN risk. Increased nonoccupational PA, low-intensity PA, and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD, with HRs (95%CIs) of 0.80 (0.73–0.88), 0.85 (0.77–0.94), and 0.85 (0.76–0.95) in the highest quartile, respectively. Conclusion: PA, including nonoccupational PA, low-intensity PA, and moderate-to-vigorous-intensity PA, was inversely associated with the risk of CKD, including DKD, HTN, and other CKD, and such associations were dose dependent.
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- 2024
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8. A genome-wide association study based on the China Kadoorie Biobank identifies genetic associations between snoring and cardiometabolic traits
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Yunqing Zhu, Zhenhuang Zhuang, Jun Lv, Dianjianyi Sun, Pei Pei, Ling Yang, Iona Y. Millwood, Robin G. Walters, Yiping Chen, Huaidong Du, Fang Liu, Rebecca Stevens, Junshi Chen, Zhengming Chen, Liming Li, Canqing Yu, and On behalf of the China Kadoorie Biobank Collaborative Group
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Biology (General) ,QH301-705.5 - Abstract
Abstract Despite the high prevalence of snoring in Asia, little is known about the genetic etiology of snoring and its causal relationships with cardiometabolic traits. Based on 100,626 Chinese individuals, a genome-wide association study on snoring was conducted. Four novel loci were identified for snoring traits mapped on SLC25A21, the intergenic region of WDR11 and FGFR, NAA25, ALDH2, and VTI1A, respectively. The novel loci highlighted the roles of structural abnormality of the upper airway and craniofacial region and dysfunction of metabolic and transport systems in the development of snoring. In the two-sample bi-directional Mendelian randomization analysis, higher body mass index, weight, and elevated blood pressure were causal for snoring, and a reverse causal effect was observed between snoring and diastolic blood pressure. Altogether, our results revealed the possible etiology of snoring in China and indicated that managing cardiometabolic health was essential to snoring prevention, and hypertension should be considered among snorers.
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- 2024
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9. Incidence and prevalence of autoimmune diseases in China: A systematic review and meta-analysis of epidemiological studies
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Olaa Mohamed-Ahmed, Lianhan Shang, Lin Wang, Zhengming Chen, Christiana Kartsonaki, and Fiona Bragg
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Autoimmunity ,Autoimmune diseases ,Autoimmune conditions ,Epidemiology ,China ,Crohn's disease ,Infectious and parasitic diseases ,RC109-216 - Abstract
Background: Autoimmune diseases account for a substantial burden of disease in high-income countries, including Europe and North America. However, their epidemiology remains under-researched in other regions. We examined the incidence and prevalence of eight autoimmune diseases in the adult Chinese population through a systematic review of epidemiological studies. Methods: We searched OvidSP MEDLINE and Google Scholar from 1995 to 2023 (inclusive) for articles on the incidence or prevalence of autoimmune thyroiditis (AT), Graves' disease (GD), type 1 diabetes mellitus (T1D), multiple sclerosis (MS), Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We included studies from mainland China, Taiwan, Hong Kong or Macau. The study is registered with PROSPERO (CRD42021225842). Findings: We retrieved 2278 records, of which 62 studies (161 estimates) were included in the systematic review, and 42 studies (101 estimates) were included in the meta-analysis. Pooled fixed-effects estimates for incidence of CD, UC, MS, T1D and SLE were 0.22 (95% CI 0.21–0.23), 1.13 (1.10–1.17), 0.28 (0.26–0.30), 2.20 (1.70–2.84) and 4.87 (4.21–5.64) per 100,000 persons, respectively. For RA, one study estimate was included, with an incidence of 15.8 per 100,000 persons. Fixed-effects estimates for the prevalence of CD, UC, MS, SLE, RA, GD and AT were 3.73 (95% CI 3.68–3.78), 16.11 (15.93–16.29), 4.08 (3.95–4.21), 93.44 (92.27–94.63), 104 (103–106), 450 (422–481) and 2322 (2057-2620), respectively, per 100,000 persons. Across all conditions, women were almost twice as likely as men to be diagnosed with an autoimmune disease. Interpretation: There is marked variation in the frequency of autoimmune diseases among Chinese adults. We estimate that 2.7–3.0% (>31 million people) of the adult Chinese population have one or more autoimmune diseases, comparable to Western populations, with the majority of the burden from autoimmune thyroid diseases and rheumatoid arthritis.
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- 2024
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10. Incidence and mortality rates of 14 site-specific infectious diseases in 10 diverse areas of China: findings from China Kadoorie Biobank, 2006-2018
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Rui Huang, Christiana Kartsonaki, Iain Turnbull, Pei Pei, Yiping Chen, Jingchao Liu, Huaidong Du, Dianjianyi Sun, Ling Yang, Maxim Barnard, Jun Lv, Canqing Yu, Junshi Chen, Liming Li, Zhengming Chen, and Fiona Bragg
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Infectious diseases ,China ,Hospitalization ,Incidence ,Mortality ,Case fatality ,Infectious and parasitic diseases ,RC109-216 - Abstract
Background: Infectious diseases remain a major global health concern, including in China, with an estimated >10 million cases of infectious disease in 2019. We describe the burden of site-specific infectious diseases among Chinese adults. Methods: From 2004 to 2008, the prospective China Kadoorie Biobank enrolled 512,726 adults aged 30-79 years from 10 diverse areas (5 rural, 5 urban) of China. During the 12 years of follow-up, 101,673 participants were hospitalized for any infectious disease. Descriptive analyses examined standardized incidence, mortality and case fatality of infections. Findings: The incidence of any infectious disease was 1856 per 100,000 person-years; respiratory tract infections (1069) were most common. The infectious disease mortality rate was 31.8 per 100,000 person-years (20.3 and 9.4 for respiratory and non-respiratory infections, respectively) and case fatality was 2.2% (2.6% and 1.6% for respiratory and non-respiratory infections, respectively). Infectious disease incidence and mortality rates were higher at older ages and in rural areas. There were no clear sex differences in infectious disease incidence rates, but mortality and case fatality rates were twice as high in men as in women. Interpretation: Infectious diseases were common in Chinese adults. The observed burden of, and disparities in, site-specific infections can inform targeted prevention efforts. Funding: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF.
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- 2024
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11. Benchmarking multi-ancestry prostate cancer polygenic risk scores in a real-world cohort.
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Yajas Shah, Scott Kulm, Jones T Nauseef, Zhengming Chen, Olivier Elemento, Kevin H Kensler, and Ravi N Sharaf
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Biology (General) ,QH301-705.5 - Abstract
Prostate cancer is a heritable disease with ancestry-biased incidence and mortality. Polygenic risk scores (PRSs) offer promising advancements in predicting disease risk, including prostate cancer. While their accuracy continues to improve, research aimed at enhancing their effectiveness within African and Asian populations remains key for equitable use. Recent algorithmic developments for PRS derivation have resulted in improved pan-ancestral risk prediction for several diseases. In this study, we benchmark the predictive power of six widely used PRS derivation algorithms, including four of which adjust for ancestry, against prostate cancer cases and controls from the UK Biobank and All of Us cohorts. We find modest improvement in discriminatory ability when compared with a simple method that prioritizes variants, clumping, and published polygenic risk scores. Our findings underscore the importance of improving upon risk prediction algorithms and the sampling of diverse cohorts.
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- 2024
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12. Temporal change in multimorbidity prevalence, clustering patterns, and the association with mortality: findings from the China Kadoorie Biobank study in Jiangsu Province
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Hao Yu, Ran Tao, Jinyi Zhou, Jian Su, Yan Lu, Yujie Hua, Jianrong Jin, Pei Pei, Canqing Yu, Dianjianyi Sun, Zhengming Chen, Liming Li, and Jun Lv
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multimorbidity ,cluster analysis ,cohort study ,prevalence ,mortality ,Public aspects of medicine ,RA1-1270 - Abstract
ObjectivesThe characteristics of multimorbidity in the Chinese population are currently unclear. We aimed to determine the temporal change in multimorbidity prevalence, clustering patterns, and the association of multimorbidity with mortality from all causes and four major chronic diseases.MethodsThis study analyzed data from the China Kadoorie Biobank study performed in Wuzhong District, Jiangsu Province. A total of 53,269 participants aged 30–79 years were recruited between 2004 and 2008. New diagnoses of 15 chronic diseases and death events were collected during the mean follow-up of 10.9 years. Yule's Q cluster analysis method was used to determine the clustering patterns of multimorbidity. A Cox proportional hazards model was used to estimate the associations of multimorbidity with mortalities.ResultsThe overall multimorbidity prevalence rate was 21.1% at baseline and 27.7% at the end of follow-up. Multimorbidity increased more rapidly during the follow-up in individuals who had a higher risk at baseline. Three main multimorbidity patterns were identified: (i) cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), (ii) respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), and (iii) mental, kidney and arthritis multimorbidity (neurasthenia, psychiatric disorders, chronic kidney disease, and rheumatoid arthritis). There were 3,433 deaths during the follow-up. The mortality risk increased by 24% with each additional disease [hazard ratio (HR) = 1.24, 95% confidence interval (CI) = 1.20–1.29]. Compared with those without multimorbidity at baseline, both cardiometabolic multimorbidity and respiratory multimorbidity were associated with increased mortality from all causes and four major chronic diseases. Cardiometabolic multimorbidity was additionally associated with mortality from cardiovascular diseases and diabetes, with HRs of 2.64 (95% CI = 2.19–3.19) and 28.19 (95% CI = 14.85–53.51), respectively. Respiratory multimorbidity was associated with respiratory disease mortality, with an HR of 9.76 (95% CI = 6.22–15.31).ConclusionThe prevalence of multimorbidity has increased substantially over the past decade. This study has revealed that cardiometabolic multimorbidity and respiratory multimorbidity have significantly increased mortality rates. These findings indicate the need to consider high-risk populations and to provide local evidence for intervention strategies and health management in economically developed regions.
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- 2024
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13. Association between health insurance cost-sharing and choice of hospital tier for cardiovascular diseases in China: a prospective cohort studyResearch in context
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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
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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.
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- 2024
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14. Using routinely collected data to determine care cascades of hypertension and type-2 diabetes management in China: a cross-sectional studyResearch in context
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Shangzhi Xiong, Wei Jiang, Yongchen Wang, Chi Hu, Jiajuan Yang, Mingjia Bao, Huinan Hou, Fan Li, Tingzhuo Liu, Xinyi Zhang, Yanqiuzi Ma, Pengpeng Ye, Qiujun Wang, Zhengming Chen, Limin Mao, David Peiris, and Maoyi Tian
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Hypertension ,Type-2 diabetes ,Care cascade ,Routinely collected data ,National Essential Public Health Service ,China ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: China’s National Essential Public Health Service Package (NEPHSP) aims to promote health for all at the primary health care level and includes a focus on hypertension and type-2 diabetes mellitus (T2DM). However, there are limited contemporary data to quantify the care cascades of hypertension and T2DM in primary health care. Methods: This cross-sectional study involved individual level linkage of routinely collected data from the NEPHSP, health insurance claims and hospital electronic health records, from four diverse regions in China, including Xiling District (central China), Wenchuan County (western), Acheng District and Jiao District (northern). We first compared numbers of people aged ≥35 with a recorded diagnosis of hypertension and T2DM against expected numbers derived from epidemiological data. We then constructed care cascades to assess the percentages (1) enrolled in the NEPHSP, (2) adherent to the follow-up care of NEPHSP, (3) receiving medication treatment, and (4) having hypertension and/or T2DM controlled. Findings: In the four regions, the total numbers of people aged ≥35 diagnosed of hypertension and T2DM from any data source were 149,176 and 50,828, respectively. This was estimated to be 46.0% (95% confidence interval [CI]: 45.8%–46.2%) and 45.6% (95% CI: 45.3%–45.9%) of the expected totals for hypertension and T2DM, respectively. Among those diagnosed, 65.4% (95% CI: 65.1%–65.6%) with hypertension and 66.1% (95% CI: 65.7%–66.5%) with T2DM were enrolled in the NEPHSP, respectively, in which 54.8% (95% CI: 54.5%–55.2%) with hypertension and 64.7% (95% CI: 64.1%–65.2%) with T2DM were adherent to the required services. Among those enrolled, the overall treatment rates were 70.8% (95% CI: 70.6%–71.1%) for hypertension and 82.2% (95% CI: 81.8%–82.6%) for T2DM. Among those treated, a further 80.9% (95% CI: 80.6%–81.2%) with hypertension and 73.9% (95% CI: 73.3%–74.4%) with T2DM achieved control. These results varied considerably across regions, with the northern sites showing relatively higher enrolment rates while the central site had higher control rates. Interpretation: Detection and control rates for hypertension and T2DM are suboptimal in these four regions of China. Further strategies are needed to improve people’s enrolment in and adherence to the NEPHSP and strengthen care delivery processes. Of note, our estimations of the diagnosis rates for each region are based on national level large epidemiological data. The interpretation of these data needs caution due to potential bias caused by regional variations. Funding: This study is funded by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Diseases funding (APP1169757), and National Natural Science Foundation of China (72074065).
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- 2024
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15. Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease
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Chengyi Ding, Linda Ng Fat, Annie Britton, Pek Kei Im, Kuang Lin, Anya Topiwala, Liming Li, Zhengming Chen, Iona Y. Millwood, Steven Bell, and Gautam Mehta
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Science - Abstract
Abstract Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions.
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- 2023
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16. Device-measured movement behaviours in over 20,000 China Kadoorie Biobank participants
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Yuanyuan Chen, Shing Chan, Derrick Bennett, Xiaofang Chen, Xianping Wu, Yalei Ke, Jun Lv, Dianjianyi Sun, Lang Pan, Pei Pei, Ling Yang, Yiping Chen, Junshi Chen, Zhengming Chen, Liming Li, Huaidong Du, Canqing Yu, Aiden Doherty, and on behalf of the China Kadoorie Biobank Collaborative Group
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Movement behaviours ,Cohort study ,Adults ,Accelerometer ,Nutritional diseases. Deficiency diseases ,RC620-627 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Movement behaviours, including physical activity, sedentary behaviour, and sleep have been shown to be associated with several chronic diseases. However, they have not been objectively measured in large-scale prospective cohort studies in low-and middle-income countries. We aim to describe the patterns of device-measured movement behaviours collected in the China Kadoorie Biobank (CKB) study. Methods During 2020 and 2021, a random subset of 25,087 surviving CKB individuals participated in the 3rd resurvey of the CKB. Among them, 22,511 (89.7%) agreed to wear an Axivity AX3 wrist-worn triaxial accelerometer for seven consecutive days to assess their habitual movement behaviours. We developed a machine-learning model to infer time spent in four movement behaviours [i.e. sleep, sedentary behaviour, light intensity physical activity (LIPA), and moderate-to-vigorous physical activity (MVPA)]. Descriptive analyses were performed for wear-time compliance and patterns of movement behaviours by different participant characteristics. Results Data from 21,897 participants (aged 65.4 ± 9.1 years; 35.4% men) were received for demographic and wear-time analysis, with a median wear-time of 6.9 days (IQR: 6.1–7.0). Among them, 20,370 eligible participants were included in movement behavior analyses. On average, they had 31.1 mg/day (total acceleration) overall activity level, accumulated 7.7 h/day (32.3%) of sleep time, 8.8 h/day (36.6%) sedentary, 5.7 h/day (23.9%) in light physical activity, and 104.4 min/day (7.2%) in moderate-to-vigorous physical activity. There was an inverse relationship between age and overall acceleration with an observed decline of 5.4 mg/day (17.4%) per additional decade. Women showed a higher activity level than men (32.3 vs 28.8 mg/day) and there was a marked geographical disparity in the overall activity level and time allocation. Conclusions This is the first large-scale accelerometer data collected among Chinese adults, which provides rich and comprehensive information about device-measured movement behaviour patterns. This resource will enhance our knowledge about the potential relevance of different movement behaviours for chronic disease in Chinese adults.
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- 2023
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17. Genetic influences on alcohol flushing in East Asian populations
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Yoonsu Cho, Kuang Lin, Su-Hyun Lee, Canqing Yu, Dan Schmidt Valle, Daniel Avery, Jun Lv, Keumji Jung, Liming Li, George Davey Smith, China Kadoorie Biobank Collaborative Group, Dianjianyi Sun, Zhengming Chen, Iona Y. Millwood, Gibran Hemani, and Robin G. Walters
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GWAS ,Alcohol ,Alcohol flushing ,ALDH2 ,ADH1B ,Heritability ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract 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. Results We identified variants in the region of ALDH2 strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 and ADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke). Conclusion This study confirms that ALDH2-rs671 and ADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.
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- 2023
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18. Association between fresh fruit consumption and the risk of chronic obstructive pulmonary disease-related hospitalization and death in Chinese adults: A prospective cohort study
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Xin Huang, Jiachen Li, Weihua Cao, Jun Lyu, Yu Guo, Pei Pei, Qingmei Xia, Huaidong Du, Yiping Chen, Yang Ling, Rene Kerosi, Rebecca Stevens, Xujun Yang, Junshi Chen, Canqing Yu, Zhengming Chen, Liming Li, on behalf of China Kadoorie Biobank, and Peifang Wei
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Medicine - Abstract
Abstract. Background:. Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease (COPD), but this is unclear in the Chinese population. We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide, population-based prospective cohort from China. Methods:. Between 2004 and 2008, the China Kadoorie Biobank recruited >0.5 million adults aged 30 to 79 years from ten diverse regions across China. After excluding individuals diagnosed with major chronic diseases and prevalent COPD, the prospective analysis included 421,428 participants. Cox regression was used to calculate the hazard ratios (HRs) for the association between fresh fruit consumption and risk of COPD-related hospitalization and death, with adjustment for established and potential confounders. Results:. During a mean follow-up of 10.9 years, 11,292 COPD hospitalization events and deaths were documented, with an overall incidence rate of 2.47/1000 person-years. Participants who consumed fresh fruit daily had a 22% lower risk of COPD-related hospitalization and death compared with non-consumers (HR = 0.78, 95% confidence interval [CI]: 0.71–0.87). The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index (BMI) (18.5 kg/m2 ≤ BMI < 24.0 kg/m2); the corresponding HRs for daily fresh fruit consumption were 0.78 (95% CI: 0.68–0.89) and 0.69 (95% CI: 0.59–0.79) compared with their counterparts, respectively. Conclusions:. High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults. Increasing fruit consumption, together with cigarette cessation and weight control, should be considered in the prevention and management of COPD.
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- 2023
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19. Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores: evidence from the China Kadoorie Biobank
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Songchun Yang, Dong Sun, Zhijia Sun, Canqing Yu, Yu Guo, Jiahui Si, Dianjianyi Sun, Yuanjie Pang, Pei Pei, Ling Yang, Iona Y. Millwood, Robin G. Walters, Yiping Chen, Huaidong Du, Zengchang Pang, Dan Schmidt, Rebecca Stevens, Robert Clarke, Junshi Chen, Zhengming Chen, Jun Lv, Liming Li, On Behalf of the China Kadoorie Biobank Collaborative Group, and Jing Ni
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Medicine - Abstract
Abstract. 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.
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- 2023
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20. Correction: Device-measured movement behaviours in over 20,000 China Kadoorie Biobank participants
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Yuanyuan Chen, Shing Chan, Derrick Bennett, Xiaofang Chen, Xianping Wu, Yalei Ke, Jun Lv, Dianjianyi Sun, Lang Pan, Pei Pei, Ling Yang, Yiping Chen, Junshi Chen, Zhengming Chen, Liming Li, Huaidong Du, Canqing Yu, Aiden Doherty, and the China Kadoorie Biobank Collaborative Group
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Nutritional diseases. Deficiency diseases ,RC620-627 ,Public aspects of medicine ,RA1-1270 - Published
- 2024
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21. Causal association between snoring and stroke: a Mendelian randomization study in a Chinese populationResearch in context
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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
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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
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- 2024
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22. Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study
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Jinxuan Li, Jianying Xu, Lan Yang, Yongjian Xu, Xiangyan Zhang, Chunxue Bai, Jian Kang, Pixin Ran, Huahao Shen, Fuqiang Wen, Kewu Huang, Wanzhen Yao, Tieying Sun, Guangliang Shan, Ting Yang, Yingxiang Lin, Jianguo Zhu, Ruiying Wang, Zhihong Shi, Jianping Zhao, Xianwei Ye, Yuanlin Song, Qiuyue Wang, Gang Hou, Yumin Zhou, Wen Li, Liren Ding, Hao Wang, Yahong Chen, Yanfei Guo, Fei Xiao, Yong Lu, Xiaoxia Peng, Biao Zhang, Zuomin Wang, Hong Zhang, Xiaoning Bu, Xiaolei Zhang, Li An, Shu Zhang, Zhixin Cao, Qingyuan Zhan, Yuanhua Yang, Lirong Liang, Bin Cao, Huaping Dai, Kian Fan Chung, Zhengming Chen, Jiang He, Sinan Wu, Dan Xiao, and Chen Wang
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Public aspects of medicine ,RA1-1270 - Abstract
BackgroundMaternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. ObjectiveThis study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). MethodsThis case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was
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- 2024
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23. Diabetes and chronic kidney disease in Chinese adults: a population-based cohort study
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Huaidong Du, Liming Li, Zhengming Chen, Junshi Chen, Lu Chen, Ling Yang, Dianjianyi Sun, Xue Wang, Jun Lv, Yiping Chen, Xiaoming Yang, Pei Pei, Canqing Yu, Jiaqiu Liu, Kexiang Shi, and Maxim Barnard
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Introduction Cohort evidence of the association of diabetes mellitus (DM) with chronic kidney disease (CKD) is limited. Previous studies often describe patients with kidney disease and diabetes as diabetic kidney disease (DKD) or CKD, ignoring other subtypes. The present study aimed to assess the prospective association of diabetes status (no diabetes, pre-diabetes, screened diabetes, previously diagnosed controlled/uncontrolled diabetes with/without antidiabetic treatment) and random plasma glucose (RPG) with CKD risk (including CKD subtypes) among Chinese adults.Research design and methods The present study included 472 545 participants from the China Kadoorie Biobank, using baseline information on diabetes and RPG. The incident CKD and its subtypes were collected through linkage with the national health insurance system during follow-up. Cox regression models were used to calculate the HR and 95% CI.Results During 11.8 years of mean follow-up, 5417 adults developed CKD. Screened plus previously diagnosed diabetes was positively associated with CKD (HR=4.52, 95% CI 4.23 to 4.83), DKD (HR=33.85, 95% CI 29.56 to 38.76), and glomerulonephritis (HR=1.66, 95% CI 1.40 to 1.97). In those with previously diagnosed diabetes, participants with uncontrolled diabetes represented higher risks of CKD, DKD, and glomerulonephritis compared with those with controlled RPG. The risk of DKD was found to rise in participants with pre-diabetes and increased with the elevated RPG level, even in those without diabetes.Conclusions Among Chinese adults, diabetes was positively associated with CKD, DKD, and glomerulonephritis. Screen-detected and uncontrolled DM had a high risk of CKD, and pre-diabetes was associated with a greater risk of DKD, highlighting the significance of lifelong glycemic management.
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- 2024
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24. Global heterogeneity in folic acid fortification policies and implications for prevention of neural tube defects and stroke: a systematic reviewResearch in context
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Matthew Quinn, Jim Halsey, Paul Sherliker, Hongchao Pan, Zhengming Chen, Derrick A. Bennett, and Robert Clarke
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Folic acid fortification ,Plasma folate ,Neural tube defects ,Stroke ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Folic acid (pteroylmonoglutamic acid) supplements are highly effective for prevention of neural tube defects (NTD) prompting implementation of mandatory or voluntary folic acid fortification for prevention of NTDs. We used plasma folate levels in population studies by country and year to compare effects of folic acid fortification types (mandatory or voluntary folic acid fortification policies) on plasma folate levels, NTD prevalence and stroke mortality rates. Methods: We conducted systematic reviews of (i) implementation of folic acid fortification in 193 countries that were member states of the World Health Organization by country and year, and (ii) estimated population mean plasma folate levels by year and type of folic acid fortification. We identified relevant English language reports published between Jan 1, 1990 and July 31, 2023 using Google Scholar, Medline, Embase and Global Health. Eligibility criteria were observational or interventional studies with >1000 participants. Studies of pregnant women or children 25 nmol/L were 100%, 15% and 7%, respectively). Among 75 countries with NTD prevalence, mean (95% CI) prevalence per 10,000 population were 4.19 (4.11–4.28), 7.61 (7.47–7.75) and 9.66 (9.52–9.81) with mandatory, voluntary and no folic acid fortification, respectively. However, age-standardised trends in stroke mortality rates were unaltered by the introduction of folic acid fortification. Interpretation: There is substantial heterogeneity in folic acid fortification policies worldwide where folic acid fortification are associated with 50–100% higher population mean plasma folate levels and 25–50% lower NTD prevalence compared with no fortification. Many thousand NTD pregnancies could be prevented yearly if all countries implemented mandatory folic acid fortification. Further trials of folic acid for stroke prevention are required in countries without effective folic acid fortification policies. Funding: Medical Research Council (UK) and British Heart Foundation.
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- 2024
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25. Sleep duration and risk of stroke and coronary heart disease: a 9-year community-based prospective study of 0.5 million Chinese adults
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Yiping Chen, Christiana Kartsonaki, Robert Clarke, Yu Guo, Huaidong Du, Canqing Yu, Ling Yang, Pei Pei, Rebecca Stevens, Sushila Burgess, Yujie Hua, Junshi Chen, Jun Lv, Liming Li, Zhengming Chen, and on behalf of the China Kadoorie Biobank Collaborative Group
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Sleep duration ,Prospective studies ,Stroke ,Myocardial infarction ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background There is uncertainty about the optimum sleep duration for risk of different subtypes of stroke and ischaemic heart disease. Methods The present analyses involved 409,156 adults in the China Kadoorie Biobank study without a prior history of coronary heart disease or stroke or insomnia symptoms. The mean age of study participants was 52 years and 59% were women. Self-reported sleep duration including daytime napping was recorded using a questionnaire. The adjusted hazard ratios (HRs) for disease outcomes associated with sleep duration were estimated by Cox proportional hazards after adjustment for confounding factors. Results The overall mean (SD) sleep duration was 7.4 (1.4) hours. The associations of sleep duration with CVD types were U-shaped, with individuals reporting 7–8 h of sleep having the lowest risks. Compared with those who typically slept 7–8 h, individuals with very short sleep duration (≤ 5 h) had adjusted HRs of 1.10 (95% CI 1.04–1.16), 1.07 (1.01–1.13), 1.19 (1.06–1.33) and 1.23 (1.10–1.37) for total stroke, ischaemic stroke (IS), Intracerebral haemorrhage (ICH) and major coronary events (MCE), respectively. Likewise, individuals with very long sleep duration (≥ 10 h) had HRs of 1.12 (1.07–1.17), 1.08 (1.03–1.14), 1.23 (1.12–1.35) and 1.22 (1.10–1.34) for the same diseases, respectively, with little differences by sex and age. The patterns were similar for all-cause mortality. Conclusions While abnormal sleep duration (≤ 6 h or ≥ 9 h) was associated with higher risks of CVD, the risks were more extreme for those reporting ≤ 5 or ≥ 10 h, respectively and such individuals should be prioritised for more intensive treatment for CVD prevention.
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- 2023
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26. Assessment of correlation between conventional anthropometric and imaging-derived measures of body fat composition: a systematic literature review and meta-analysis of observational studies
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Sofia Mouchti, Josefina Orliacq, Gillian Reeves, and Zhengming Chen
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Adiposity ,Anthropometric ,Imaging ,MRI ,DXA ,Correlation ,Medical technology ,R855-855.5 - Abstract
Abstract Background In studies of the association of adiposity with disease risk, widely used anthropometric measures of adiposity (e.g. body-mass-index [BMI], waist circumference [WC], waist-hip ratio [WHR]) are simple and inexpensive to implement at scale. In contrast, imaging-based techniques (e.g. magnetic resonance imaging [MRI] and dual x-ray absorptiometry [DXA]) are expensive and labour intensive, but can provide more accurate quantification of body fat composition. There is, however, limited evidence about the relationship between conventional and imaging-derived measures of adiposity. Methods We searched Scopus and Web of Science for published reports in English of conventional versus imaging-derived measurements of adiposity. We identified 42 articles (MRI = 22; DXA = 20) that met selection criteria, involving 42,556 (MRI = 15,130; DXA = 27,426) individuals recruited from community or hospital settings. Study-specific correlation coefficients (r) were transformed using Fisher’s Z transformation, and meta-analysed to yield weighted average correlations, both overall and by ancestry, sex and age, where feasible. Publication bias was investigated using funnel plots and Egger’s test. Results Overall, 98% of participants were 18 + years old, 85% male and 95% White. BMI and WC were most strongly correlated with imaging-derived total abdominal (MRI-derived: r = 0.88-; DXA-derived: 0.50–0.86) and subcutaneous abdominal fat (MRI-derived: 0.83–0.85), but were less strongly correlated with visceral abdominal fat (MRI-derived: 0.76-0.79; DXA-derived: 0.80) and with DXA-derived %body fat (0.76). WHR was, at best, strongly correlated with imaging-derived total abdominal (MRI-derived: 0.60; DXA-derived: 0.13), and visceral abdominal fat (MRI-derived: 0.67; DXA-derived: 0.65), and moderately with subcutaneous abdominal (MRI-derived: 0.54), and with DXA-derived %body fat (0.58). All conventional adiposity measures were at best moderately correlated with hepatic fat (MRI-derived: 0.36–0.43). In general, correlations were stronger in women than in men, in Whites than in non-Whites, and in those aged 18 + years. Conclusions In this meta-analysis, BMI and WC, but not WHR, were very strongly correlated with imaging-derived total and subcutaneous abdominal fat. By comparison, all three measures were moderately or strongly correlated with imaging-based visceral abdominal fat, with WC showing the greatest correlation. No anthropometric measure was substantially correlated with hepatic fat. Further larger studies are needed to compare these measures within the same study population, and to assess their relevance for disease risks in diverse populations.
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- 2023
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27. Genetic and healthy lifestyle factors in relation to the incidence and prognosis of severe liver disease in the Chinese population
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Yuanjie Pang, Jun Lv, Christiana Kartsonaki, Canqing Yu, Yu Guo, Yiping Chen, Ling Yang, Iona Y. Millwood, Robin G. Walters, Silu Lv, Sushila Burgess, Sam Sansome, Junshi Chen, Zhengming Chen, Liming Li, and Jing Ni
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Medicine - Abstract
Abstract. Background:. Severe liver disease (SLD), including cirrhosis and liver cancer, constitutes a major disease burden in China. We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD. Methods:. The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years. The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HRs) for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors (smoking, alcohol, physical activity, and central adiposity). Additionally, the contribution of genetic risk for hepatitis B virus (HBV, assessed by genetic variants in major histocompatibility complex, class II, DP/DQ [HLA-DP/DQ] genes) was also estimated. Results:. Compared with those with 0-1 healthy lifestyle factor, participants with 2, 3, and 4 factors had 12% (HR 0.88 [95% confidence interval [CI] 0.85, 0.92]), 26% (HR 0.74 [95%CI: 0.69, 0.79]), and 44% (HR 0.56 [95%CI: 0.48, 0.65]) lower risks of SLD, respectively. Inverse associations were observed among participants with both low and high genetic risks (HR per 1-point increase 0.83 [95%CI: 0.74, 0.94] and 0.91 [95%CI: 0.82, 1.02], respectively; Pinteraction = 0.51), although with a non-significant trend among those with a high genetic risk. Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk. Despite the limited power, healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk (HR 0.59 [95%CI: 0.37, 0.96]). Conclusions:. Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk. Moreover, it is also important for improving the prognosis of SLD in individuals with a low genetic risk. Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis, particularly among individuals with a high genetic risk.
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- 2023
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28. Lung cancer risk score for ever and never smokers in China
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Zhimin Ma, Jun Lv, Meng Zhu, Canqing Yu, Hongxia Ma, Guangfu Jin, Yu Guo, Zheng Bian, Ling Yang, Yiping Chen, Zhengming Chen, Zhibin Hu, Liming Li, and Hongbing Shen
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early‐onset cancer ,lung cancer screening ,lung cancer ,never smokers ,prediction model ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Most lung cancer risk prediction models were developed in European and North‐American cohorts of smokers aged ≥ 55 years, while less is known about risk profiles in Asia, especially for never smokers or individuals aged < 50 years. Hence, we aimed to develop and validate a lung cancer risk estimate tool for ever and never smokers across a wide age range. Methods Based on the China Kadoorie Biobank cohort, we first systematically selected the predictors and explored the nonlinear association of predictors with lung cancer risk using restricted cubic splines. Then, we separately developed risk prediction models to construct a lung cancer risk score (LCRS) in 159,715 ever smokers and 336,526 never smokers. The LCRS was further validated in an independent cohort over a median follow‐up of 13.6 years, consisting of 14,153 never smokers and 5,890 ever smokers. Results A total of 13 and 9 routinely available predictors were identified for ever and never smokers, respectively. Of these predictors, cigarettes per day and quit years showed nonlinear associations with lung cancer risk (Pnon‐linear < 0.001). The curve of lung cancer incidence increased rapidly above 20 cigarettes per day and then was relatively flat until approximately 30 cigarettes per day. We also observed that lung cancer risk declined sharply within the first 5 years of quitting, and then continued to decrease but at a slower rate in the subsequent years. The 6‐year area under the receiver operating curve for the ever and never smokers’ models were respectively 0.778 and 0.733 in the derivation cohort, and 0.774 and 0.759 in the validation cohort. In the validation cohort, the 10‐year cumulative incidence of lung cancer was 0.39% and 2.57% for ever smokers with low (< 166.2) and intermediate‐high LCRS (≥ 166.2), respectively. Never smokers with a high LCRS (≥ 21.2) had a higher 10‐year cumulative incidence rate than those with a low LCRS (< 21.2; 1.05% vs. 0.22%). An online risk evaluation tool (LCKEY; http://ccra.njmu.edu.cn/lckey/web) was developed to facilitate the use of LCRS. Conclusions The LCRS can be an effective risk assessment tool designed for ever and never smokers aged 30 to 80 years.
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- 2023
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29. BMI and well-being in people of East Asian and European ancestry: a Mendelian randomisation study
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Jessica O’Loughlin, Francesco Casanova, Amanda Hughes, Zammy Fairhurst-Hunter, Liming Li, Zhengming Chen, China Kadoorie Biobank Collaborative Group, Jack Bowden, Ed Watkins, Rachel M. Freathy, Laura D. Howe, Robin G. Walters, and Jessica Tyrrell
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Previous studies have linked higher body mass index (BMI) to lower subjective well-being in adult European ancestry populations. However, our understanding of these relationships across different populations is limited. Here, we investigated the association between BMI and well-being in people of (a) East Asian and (b) European ancestry in the China Kadoorie Biobank (CKB) and UK Biobank (UKB), respectively. Mendelian randomisation (MR) methods were used to test the relationship between BMI with (a) health satisfaction and (b) life satisfaction. One-sample MR enabled us to test effects in men and women separately and to test the role of cultural contexts by stratifying our analyses by urban and rural home location in both China and the UK. Further, we implemented a control function method to test the linearity of the BMI-well-being relationship. We found evidence of different associations between BMI and well-being in individuals of East Asian versus European ancestry. For example, a genetically instrumented higher BMI tentatively associated with higher health satisfaction in people of East Asian ancestry, especially in females (ß: 0.041, 95% CI: 0.002, 0.081). In contrast, there was a robust inverse association between higher genetically instrumented BMI and health satisfaction in all European ancestry UKB participants (ß: −0.183, 95% CI: −0.200, −0.165, P difference
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- 2023
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30. Duration-dependent impact of cardiometabolic diseases and multimorbidity on all-cause and cause-specific mortality: a prospective cohort study of 0.5 million participants
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Yuting Han, Yizhen Hu, Canqing Yu, Dianjianyi Sun, Yuanjie Pang, Pei Pei, Ling Yang, Yiping Chen, Huaidong Du, Jingchao Liu, Dan Schmidt, Daniel Avery, Junshi Chen, Zhengming Chen, Liming Li, and Jun Lv
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Cardiometabolic disease ,Multimorbidity ,Mortality ,Prospective cohort ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background The association of incident cardiometabolic multimorbidity (CMM) with mortality risk is rarely studied, and neither are the durations of cardiometabolic diseases (CMDs). Whether the association patterns of CMD durations with mortality change as individuals progress from one CMD to CMM is unclear. Methods Data from China Kadoorie Biobank of 512,720 participants aged 30–79 was used. CMM was defined as the simultaneous presence of two or more CMDs of interest, including diabetes, ischemic heart disease, and stroke. Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the duration-dependent associations of CMDs and CMM with all-cause and cause-specific mortality. All information on exposures of interest was updated during follow-up. Results During a median follow-up of 12.1 years, 99,770 participants experienced at least one incident CMD, and 56,549 deaths were documented. Among 463,178 participants free of three CMDs at baseline, compared with no CMD during follow-up, the adjusted HRs (95% CIs) between CMM and all-cause mortality, mortality from circulatory system diseases, respiratory system diseases, cancer, and other causes were 2.93 (2.80–3.07), 5.05 (4.74–5.37), 2.72 (2.35–3.14), 1.30 (1.16–1.45), and 2.30 (2.02–2.61), respectively. All CMDs exhibited a high mortality risk in the first year of diagnosis. Subsequently, with prolonged disease duration, mortality risk increased for diabetes, decreased for IHD, and sustained at a high level for stroke. With the presence of CMM, the above association estimates inflated, but the pattern of which remained. Conclusion Among Chinese adults, mortality risk increased with the number of the CMDs and changed with prolonged disease duration, the patterns of which varied among the three CMDs.
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- 2023
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31. Development, validation, and evaluation of a risk assessment tool for personalized screening of gastric cancer in Chinese populations
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Xia Zhu, Jun Lv, Meng Zhu, Caiwang Yan, Bin Deng, Canqing Yu, Yu Guo, Jing Ni, Qiang She, Tianpei Wang, Jiayu Wang, Yue Jiang, Jiaping Chen, Dong Hang, Ci Song, Xuefeng Gao, Jian Wu, Juncheng Dai, Hongxia Ma, Ling Yang, Yiping Chen, Mingyang Song, Qingyi Wei, Zhengming Chen, Zhibin Hu, Hongbing Shen, Yanbing Ding, Liming Li, and Guangfu Jin
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Gastric cancer ,Risk prediction ,Risk stratification ,Screening ,Personalized prevention ,Medicine - Abstract
Abstract Background Effective risk prediction models are lacking for personalized endoscopic screening of gastric cancer (GC). We aimed to develop, validate, and evaluate a questionnaire-based GC risk assessment tool for risk prediction and stratification in the Chinese population. Methods In this three-stage multicenter study, we first selected eligible variables by Cox regression models and constructed a GC risk score (GCRS) based on regression coefficients in 416,343 subjects (aged 40–75 years) from the China Kadoorie Biobank (CKB, development cohort). In the same age range, we validated the GCRS effectiveness in 13,982 subjects from another independent Changzhou cohort (validation cohort) as well as in 5348 subjects from an endoscopy screening program in Yangzhou. Finally, we categorized participants into low (bottom 20%), intermediate (20–80%), and high risk (top 20%) groups by the GCRS distribution in the development cohort. Results The GCRS using 11 questionnaire-based variables demonstrated a Harrell’s C-index of 0.754 (95% CI, 0.745–0.762) and 0.736 (95% CI, 0.710–0.761) in the two cohorts, respectively. In the validation cohort, the 10-year risk was 0.34%, 1.05%, and 4.32% for individuals with a low (≤ 13.6), intermediate (13.7~30.6), and high (≥ 30.7) GCRS, respectively. In the endoscopic screening program, the detection rate of GC varied from 0.00% in low-GCRS individuals, 0.27% with intermediate GCRS, to 2.59% with high GCRS. A proportion of 81.6% of all GC cases was identified from the high-GCRS group, which represented 28.9% of all the screened participants. Conclusions The GCRS can be an effective risk assessment tool for tailored endoscopic screening of GC in China. Risk Evaluation for Stomach Cancer by Yourself (RESCUE), an online tool was developed to aid the use of GCRS.
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- 2023
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32. Development of a prediction model to identify undiagnosed chronic obstructive pulmonary disease patients in primary care settings in China
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Buyu Zhang, Dong Sun, Hongtao Niu, Fen Dong, Jun Lyu, Yu Guo, Huaidong Du, Yalin Chen, Junshi Chen, Weihua Cao, Ting Yang, Canqing Yu, Zhengming Chen, Liming Li, Peifang Wei, Xiangxiang Pan, and on behalf of the China Kadoorie Biobank Collaborative Group
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Medicine - Abstract
Abstract. Background:. At present, a large number of chronic obstructive pulmonary disease (COPD) patients are undiagnosed in China. Thus, this study aimed to develop a simple prediction model as a screening tool to identify patients at risk for COPD. Methods:. The study was based on the data of 22,943 subjects aged 30 to 79 years and enrolled in the second resurvey of China Kadoorie Biobank during 2012 and 2013 in China. We stepwisely selected the predictors using logistic regression model. Then we tested the model validity through P–P graph, area under the receiver operating characteristic curve (AUROC), ten-fold cross validation and an external validation in a sample of 3492 individuals from the Enjoying Breathing Program in China. Results:. The final prediction model involved 14 independent variables, including age, sex, location (urban/rural), region, educational background, smoking status, smoking amount (pack-years), years of exposure to air pollution by cooking fuel, family history of COPD, history of tuberculosis, body mass index, shortness of breath, sputum and wheeze. The model showed an area under curve (AUC) of 0.72 (95% confidence interval [CI]: 0.72–0.73) for detecting undiagnosed COPD patients, with the cutoff of predicted probability of COPD=0.22, presenting a sensitivity of 70.13% and a specificity of 62.25%. The AUROC value for screening undiagnosed patients with clinically significant COPD was 0.68 (95% CI: 0.66–0.69). Moreover, the ten-fold cross validation reported an AUC of 0.72 (95% CI: 0.71–0.73), and the external validation presented an AUC of 0.69 (95% CI: 0.68–0.71). Conclusion:. This prediction model can serve as a first-stage screening tool for undiagnosed COPD patients in primary care settings.
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- 2023
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33. Healthy lifestyle, DNA methylation age acceleration, and incident risk of coronary heart disease
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Jiahui Si, Lu Chen, Canqing Yu, Yu Guo, Dianjianyi Sun, Yuanjie Pang, Iona Y. Millwood, Robin G. Walters, Ling Yang, Yiping Chen, Huaidong Du, Shixian Feng, Xiaoming Yang, Daniel Avery, Junshi Chen, Zhengming Chen, Liming Liang, Liming Li, Jun Lv, and the China Kadoorie Biobank Collaborative Group
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Epigenetic age ,Cardiovascular health ,Coronary artery disease ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background DNA methylation clocks emerged as a tool to determine biological aging and have been related to mortality and age-related diseases. Little is known about the association of DNA methylation age (DNAm age) with coronary heart disease (CHD), especially in the Asian population. Results Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip for 491 incident CHD cases and 489 controls in the prospective China Kadoorie Biobank. We calculated the methylation age using a prediction model developed among Chinese. The correlation between chronological age and DNAm age was 0.90. DNA methylation age acceleration (Δage) was defined as the residual of regressing DNA methylation age on the chronological age. After adjustment for multiple risk factors of CHD and cell type proportion, compared with participants in the bottom quartile of Δage, the OR (95% CI) for CHD was 1.84 (1.17, 2.89) for participants in the top quartile. One SD increment in Δage was associated with 30% increased risk of CHD (OR = 1.30; 95% CI 1.09, 1.56; Ptrend = 0.003). The average number of cigarette equivalents consumed per day and waist-to-hip ratio were positively associated with Δage; red meat consumption was negatively associated with Δage, characterized by accelerated aging in those who never or rarely consumed red meat (all P
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- 2023
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34. Long-term ambient air pollution exposure and cardio-respiratory disease in China: findings from a prospective cohort study
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Neil Wright, Katherine Newell, Ka Hung Chan, Simon Gilbert, Alex Hacker, Yan Lu, Yu Guo, Pei Pei, Canqing Yu, Jun Lv, Junshi Chen, Liming Li, Om Kurmi, Zhengming Chen, Kin Bong Hubert Lam, and Christiana Kartsonaki
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Air pollution ,Cardiovascular disease ,Respiratory disease ,Industrial medicine. Industrial hygiene ,RC963-969 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Existing evidence on long-term ambient air pollution (AAP) exposure and risk of cardio-respiratory diseases in China is mainly on mortality, and based on area average concentrations from fixed-site monitors for individual exposures. Substantial uncertainty persists, therefore, about the shape and strength of the relationship when assessed using more personalised individual exposure data. We aimed to examine the relationships between AAP exposure and risk of cardio-respiratory diseases using predicted local levels of AAP. Methods A prospective study included 50,407 participants aged 30–79 years from Suzhou, China, with concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), fine (PM2.5), and inhalable (PM10) particulate matter, ozone (O3) and carbon monoxide (CO) and incident cases of cardiovascular disease (CVD) (n = 2,563) and respiratory disease (n = 1,764) recorded during 2013–2015. Cox regression models with time-dependent covariates were used to estimate adjusted hazard ratios (HRs) for diseases associated with local-level concentrations of AAP exposure, estimated using Bayesian spatio–temporal modelling. Results The study period of 2013–2015 included a total of 135,199 person-years of follow-up for CVD. There was a positive association of AAP, particularly SO2 and O3, with risk of major cardiovascular and respiratory diseases. Each 10 µg/m3 increase in SO2 was associated with adjusted hazard ratios (HRs) of 1.07 (95% CI: 1.02, 1.12) for CVD, 1.25 (1.08, 1.44) for COPD and 1.12 (1.02, 1.23) for pneumonia. Similarly, each 10 µg/m3 increase in O3 was associated with adjusted HR of 1.02 (1.01, 1.03) for CVD, 1.03 (1.02, 1.05) for all stroke, and 1.04 (1.02, 1.06) for pneumonia. Conclusions Among adults in urban China, long-term exposure to ambient air pollution is associated with a higher risk of cardio-respiratory disease.
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- 2023
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35. Mendelian randomisation study of body composition and depression in people of East Asian ancestry highlights potential setting-specific causality
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Jessica O’Loughlin, Francesco Casanova, Zammy Fairhurst-Hunter, Amanda Hughes, Jack Bowden, Edward R. Watkins, Rachel M. Freathy, Iona Y. Millwood, Kuang Lin, Zhengming Chen, Liming Li, Jun Lv, China Kadoorie Biobank Collaborative Group, Robin G. Walters, Laura D. Howe, Karoline Kuchenbaecker, and Jessica Tyrrell
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Mendelian randomisation ,BMI ,Depression ,East Asian ancestry ,Public health ,Setting-specific causality ,Medicine - Abstract
Abstract Background Extensive evidence links higher body mass index (BMI) to higher odds of depression in people of European ancestry. However, our understanding of the relationship across different settings and ancestries is limited. Here, we test the relationship between body composition and depression in people of East Asian ancestry. Methods Multiple Mendelian randomisation (MR) methods were used to test the relationship between (a) BMI and (b) waist-hip ratio (WHR) with depression. Firstly, we performed two-sample MR using genetic summary statistics from a recent genome-wide association study (GWAS) of depression (with 15,771 cases and 178,777 controls) in people of East Asian ancestry. We selected 838 single nucleotide polymorphisms (SNPs) correlated with BMI and 263 SNPs correlated with WHR as genetic instrumental variables to estimate the causal effect of BMI and WHR on depression using the inverse-variance weighted (IVW) method. We repeated these analyses stratifying by home location status: China versus UK or USA. Secondly, we performed one-sample MR in the China Kadoorie Biobank (CKB) in 100,377 participants. This allowed us to test the relationship separately in (a) males and females and (b) urban and rural dwellers. We also examined (c) the linearity of the BMI-depression relationship. Results Both MR analyses provided evidence that higher BMI was associated with lower odds of depression. For example, a genetically-instrumented 1-SD higher BMI in the CKB was associated with lower odds of depressive symptoms [OR: 0.77, 95% CI: 0.63, 0.95]. There was evidence of differences according to place of residence. Using the IVW method, higher BMI was associated with lower odds of depression in people of East Asian ancestry living in China but there was no evidence for an association in people of East Asian ancestry living in the USA or UK. Furthermore, higher genetic BMI was associated with differential effects in urban and rural dwellers within China. Conclusions This study provides the first MR evidence for an inverse relationship between BMI and depression in people of East Asian ancestry. This contrasts with previous findings in European populations and therefore the public health response to obesity and depression is likely to need to differ based on sociocultural factors for example, ancestry and place of residence. This highlights the importance of setting-specific causality when using genetic causal inference approaches and data from diverse populations to test hypotheses. This is especially important when the relationship tested is not purely biological and may involve sociocultural factors.
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- 2023
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36. Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults
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Yanbo Zhang, Canqing Yu, Shuohua Chen, Zhouzheng Tu, Mengyi Zheng, Jun Lv, Guodong Wang, Yan Liu, Jiaxin Yu, Yu Guo, Ling Yang, Yiping Chen, Kunquan Guo, Kun Yang, Handong Yang, Yanfeng Zhou, Yiwen Jiang, Xiaomin Zhang, Meian He, Gang Liu, Zhengming Chen, Tangchun Wu, Shouling Wu, Liming Li, An Pan, and Jing Ni
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Medicine - Abstract
Abstract. Background:. Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. Methods:. A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004–2018), Dongfeng-Tongji cohort (2008–2018), and Kailuan study (2006–2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. Results:. During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10–14 vs. 0–6 were 0.52 (0.41–0.67), 0.44 (0.37–0.53), 0.54 (0.45–0.66), and 0.86 (0.64–1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. Conclusions:. ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
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- 2023
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37. Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection
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Liuliu Yang, Yuling Han, Ting Zhou, Lauretta A. Lacko, Mohsan Saeed, Christina Tan, Ron Danziger, Jiajun Zhu, Zeping Zhao, Clare Cahir, Alice Maria Giani, Yang Li, Xue Dong, Dorota Moroziewicz, Daniel Paull, Zhengming Chen, Aaron Zhong, Scott A. Noggle, Charles M. Rice, Qibin Qi, Todd Evans, and Shuibing Chen
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Stem cells research ,Virology ,Science - Abstract
Summary: Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in NDUFA4, harboring risk versus non-risk alleles of SNPs (rs917172 and rs12386620) or having deletions in the NDUFA4 cis-regulatory region with ZIKV. We found that loss/reduction of NDUFA4 suppressed ZIKV infection in trophectoderm cells. This study validated our published hiPSC array-based system as a useful platform for GWAS and confirmed the role of NDUFA4 as a susceptibility locus for ZIKV in disease-relevant trophectoderm cells.
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- 2023
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38. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
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Stavroula Kanoni, Sarah E. Graham, Yuxuan Wang, Ida Surakka, Shweta Ramdas, Xiang Zhu, Shoa L. Clarke, Konain Fatima Bhatti, Sailaja Vedantam, Thomas W. Winkler, Adam E. Locke, Eirini Marouli, Greg J. M. Zajac, Kuan-Han H. Wu, Ioanna Ntalla, Qin Hui, Derek Klarin, Austin T. Hilliard, Zeyuan Wang, Chao Xue, Gudmar Thorleifsson, Anna Helgadottir, Daniel F. Gudbjartsson, Hilma Holm, Isleifur Olafsson, Mi Yeong Hwang, Sohee Han, Masato Akiyama, Saori Sakaue, Chikashi Terao, Masahiro Kanai, Wei Zhou, Ben M. Brumpton, Humaira Rasheed, Aki S. Havulinna, Yogasudha Veturi, Jennifer Allen Pacheco, Elisabeth A. Rosenthal, Todd Lingren, QiPing Feng, Iftikhar J. Kullo, Akira Narita, Jun Takayama, Hilary C. Martin, Karen A. Hunt, Bhavi Trivedi, Jeffrey Haessler, Franco Giulianini, Yuki Bradford, Jason E. Miller, Archie Campbell, Kuang Lin, Iona Y. Millwood, Asif Rasheed, George Hindy, Jessica D. Faul, Wei Zhao, David R. Weir, Constance Turman, Hongyan Huang, Mariaelisa Graff, Ananyo Choudhury, Dhriti Sengupta, Anubha Mahajan, Michael R. Brown, Weihua Zhang, Ketian Yu, Ellen M. Schmidt, Anita Pandit, Stefan Gustafsson, Xianyong Yin, Jian’an Luan, Jing-Hua Zhao, Fumihiko Matsuda, Hye-Mi Jang, Kyungheon Yoon, Carolina Medina-Gomez, Achilleas Pitsillides, Jouke Jan Hottenga, Andrew R. Wood, Yingji Ji, Zishan Gao, Simon Haworth, Noha A. Yousri, Ruth E. Mitchell, Jin Fang Chai, Mette Aadahl, Anne A. Bjerregaard, Jie Yao, Ani Manichaikul, Chii-Min Hwu, Yi-Jen Hung, Helen R. Warren, Julia Ramirez, Jette Bork-Jensen, Line L. Kårhus, Anuj Goel, Maria Sabater-Lleal, Raymond Noordam, Pala Mauro, Floris Matteo, Aaron F. McDaid, Pedro Marques-Vidal, Matthias Wielscher, Stella Trompet, Naveed Sattar, Line T. Møllehave, Matthias Munz, Lingyao Zeng, Jianfeng Huang, Bin Yang, Alaitz Poveda, Azra Kurbasic, Claudia Lamina, Lukas Forer, Markus Scholz, Tessel E. Galesloot, Jonathan P. Bradfield, Sanni E. Ruotsalainen, EWarwick Daw, Joseph M. Zmuda, Jonathan S. Mitchell, Christian Fuchsberger, Henry Christensen, Jennifer A. Brody, Miguel Vazquez-Moreno, Mary F. Feitosa, Mary K. Wojczynski, Zhe Wang, Michael H. Preuss, Massimo Mangino, Paraskevi Christofidou, Niek Verweij, Jan W. Benjamins, Jorgen Engmann, Noah L. Tsao, Anurag Verma, Roderick C. Slieker, Ken Sin Lo, Nuno R. Zilhao, Phuong Le, Marcus E. Kleber, Graciela E. Delgado, Shaofeng Huo, Daisuke D. Ikeda, Hiroyuki Iha, Jian Yang, Jun Liu, Ayşe Demirkan, Hampton L. Leonard, Jonathan Marten, Mirjam Frank, Börge Schmidt, Laura J. Smyth, Marisa Cañadas-Garre, Chaolong Wang, Masahiro Nakatochi, Andrew Wong, Nina Hutri-Kähönen, Xueling Sim, Rui Xia, Alicia Huerta-Chagoya, Juan Carlos Fernandez-Lopez, Valeriya Lyssenko, Suraj S. Nongmaithem, Swati Bayyana, Heather M. Stringham, Marguerite R. Irvin, Christopher Oldmeadow, Han-Na Kim, Seungho Ryu, Paul R. H. J. Timmers, Liubov Arbeeva, Rajkumar Dorajoo, Leslie A. Lange, Gauri Prasad, Laura Lorés-Motta, Marc Pauper, Jirong Long, Xiaohui Li, Elizabeth Theusch, Fumihiko Takeuchi, Cassandra N. Spracklen, Anu Loukola, Sailalitha Bollepalli, Sophie C. Warner, Ya Xing Wang, Wen B. Wei, Teresa Nutile, Daniela Ruggiero, Yun Ju Sung, Shufeng Chen, Fangchao Liu, Jingyun Yang, Katherine A. Kentistou, Bernhard Banas, Giuseppe Giovanni Nardone, Karina Meidtner, Lawrence F. Bielak, Jennifer A. Smith, Prashantha Hebbar, Aliki-Eleni Farmaki, Edith Hofer, Maoxuan Lin, Maria Pina Concas, Simona Vaccargiu, Peter J. van der Most, Niina Pitkänen, Brian E. Cade, Sander W. van der Laan, Kumaraswamy Naidu Chitrala, Stefan Weiss, Amy R. Bentley, Ayo P. Doumatey, Adebowale A. Adeyemo, Jong Young Lee, Eva R. B. Petersen, Aneta A. Nielsen, Hyeok Sun Choi, Maria Nethander, Sandra Freitag-Wolf, Lorraine Southam, Nigel W. Rayner, Carol A. Wang, Shih-Yi Lin, Jun-Sing Wang, Christian Couture, Leo-Pekka Lyytikäinen, Kjell Nikus, Gabriel Cuellar-Partida, Henrik Vestergaard, Bertha Hidalgo, Olga Giannakopoulou, Qiuyin Cai, Morgan O. Obura, Jessica van Setten, Xiaoyin Li, Jingjing Liang, Hua Tang, Natalie Terzikhan, Jae Hun Shin, Rebecca D. Jackson, Alexander P. Reiner, Lisa Warsinger Martin, Zhengming Chen, Liming Li, Takahisa Kawaguchi, Joachim Thiery, Joshua C. Bis, Lenore J. Launer, Huaixing Li, Mike A. Nalls, Olli T. Raitakari, Sahoko Ichihara, Sarah H. Wild, Christopher P. Nelson, Harry Campbell, Susanne Jäger, Toru Nabika, Fahd Al-Mulla, Harri Niinikoski, Peter S. Braund, Ivana Kolcic, Peter Kovacs, Tota Giardoglou, Tomohiro Katsuya, Dominique de Kleijn, Gert J. de Borst, Eung Kweon Kim, Hieab H. H. Adams, M. Arfan Ikram, Xiaofeng Zhu, Folkert W. Asselbergs, Adriaan O. Kraaijeveld, Joline W. J. Beulens, Xiao-Ou Shu, Loukianos S. Rallidis, Oluf Pedersen, Torben Hansen, Paul Mitchell, Alex W. Hewitt, Mika Kähönen, Louis Pérusse, Claude Bouchard, Anke Tönjes, Yii-Der Ida Chen, Craig E. Pennell, Trevor A. Mori, Wolfgang Lieb, Andre Franke, Claes Ohlsson, Dan Mellström, Yoon Shin Cho, Hyejin Lee, Jian-Min Yuan, Woon-Puay Koh, Sang Youl Rhee, Jeong-Taek Woo, Iris M. Heid, Klaus J. Stark, Martina E. Zimmermann, Henry Völzke, Georg Homuth, Michele K. Evans, Alan B. Zonderman, Ozren Polasek, Gerard Pasterkamp, Imo E. Hoefer, Susan Redline, Katja Pahkala, Albertine J. Oldehinkel, Harold Snieder, Ginevra Biino, Reinhold Schmidt, Helena Schmidt, Stefania Bandinelli, George Dedoussis, Thangavel Alphonse Thanaraj, Sharon L. R. Kardia, Patricia A. Peyser, Norihiro Kato, Matthias B. Schulze, Giorgia Girotto, Carsten A. Böger, Bettina Jung, Peter K. Joshi, David A. Bennett, Philip L. De Jager, Xiangfeng Lu, Vasiliki Mamakou, Morris Brown, Mark J. Caulfield, Patricia B. Munroe, Xiuqing Guo, Marina Ciullo, Jost B. Jonas, Nilesh J. Samani, Jaakko Kaprio, Päivi Pajukanta, Teresa Tusié-Luna, Carlos A. Aguilar-Salinas, Linda S. Adair, Sonny Augustin Bechayda, H. Janaka de Silva, Ananda R. Wickremasinghe, Ronald M. Krauss, Jer-Yuarn Wu, Wei Zheng, Anneke Iden Hollander, Dwaipayan Bharadwaj, Adolfo Correa, James G. Wilson, Lars Lind, Chew-Kiat Heng, Amanda E. Nelson, Yvonne M. Golightly, James F. Wilson, Brenda Penninx, Hyung-Lae Kim, John Attia, Rodney J. Scott, D. C. Rao, Donna K. Arnett, Steven C. Hunt, Mark Walker, Heikki A. Koistinen, Giriraj R. Chandak, Josep M. Mercader, Maria C. Costanzo, Dongkeun Jang, Noël P. Burtt, Clicerio Gonzalez Villalpando, Lorena Orozco, Myriam Fornage, EShyong Tai, Rob M. van Dam, Terho Lehtimäki, Nish Chaturvedi, Mitsuhiro Yokota, Jianjun Liu, Dermot F. Reilly, Amy Jayne McKnight, Frank Kee, Karl-Heinz Jöckel, Mark I. McCarthy, Colin N. A. Palmer, Veronique Vitart, Caroline Hayward, Eleanor Simonsick, Cornelia M. van Duijn, Zi-Bing Jin, Jia Qu, Haretsugu Hishigaki, Xu Lin, Winfried März, Vilmundur Gudnason, Jean-Claude Tardif, Guillaume Lettre, Leen M.‘t Hart, Petra J. M. Elders, Scott M. Damrauer, Meena Kumari, Mika Kivimaki, Pim van der Harst, Tim D. Spector, Ruth J. F. Loos, Michael A. Province, Esteban J. Parra, Miguel Cruz, Bruce M. Psaty, Ivan Brandslund, Peter P. Pramstaller, Charles N. Rotimi, Kaare Christensen, Samuli Ripatti, Elisabeth Widén, Hakon Hakonarson, Struan F. A. Grant, Lambertus A. L. M. Kiemeney, Jacqueline de Graaf, Markus Loeffler, Florian Kronenberg, Dongfeng Gu, Jeanette Erdmann, Heribert Schunkert, Paul W. Franks, Allan Linneberg, J. Wouter Jukema, Amit V. Khera, Minna Männikkö, Marjo-Riitta Jarvelin, Zoltan Kutalik, Cucca Francesco, Dennis O. Mook-Kanamori, Ko Willems van Dijk, Hugh Watkins, David P. Strachan, Niels Grarup, Peter Sever, Neil Poulter, Lee-Ming Chuang, Jerome I. Rotter, Thomas M. Dantoft, Fredrik Karpe, Matt J. Neville, Nicholas J. Timpson, Ching-Yu Cheng, Tien-Yin Wong, Chiea Chuen Khor, Hengtong Li, Charumathi Sabanayagam, Annette Peters, Christian Gieger, Andrew T. Hattersley, Nancy L. Pedersen, Patrik K. E. Magnusson, Dorret I. Boomsma, Allegonda H. M. Willemsen, LAdrienne Cupples, Joyce B. J. van Meurs, Mohsen Ghanbari, Penny Gordon-Larsen, Wei Huang, Young Jin Kim, Yasuharu Tabara, Nicholas J. Wareham, Claudia Langenberg, Eleftheria Zeggini, Johanna Kuusisto, Markku Laakso, Erik Ingelsson, Goncalo Abecasis, John C. Chambers, Jaspal S. Kooner, Paul S. de Vries, Alanna C. Morrison, Scott Hazelhurst, Michèle Ramsay, Kari E. North, Martha Daviglus, Peter Kraft, Nicholas G. Martin, John B. Whitfield, Shahid Abbas, Danish Saleheen, Robin G. Walters, Michael V. Holmes, Corri Black, Blair H. Smith, Aris Baras, Anne E. Justice, Julie E. Buring, Paul M. Ridker, Daniel I. Chasman, Charles Kooperberg, Gen Tamiya, Masayuki Yamamoto, David A. van Heel, Richard C. Trembath, Wei-Qi Wei, Gail P. Jarvik, Bahram Namjou, M. Geoffrey Hayes, Marylyn D. Ritchie, Pekka Jousilahti, Veikko Salomaa, Kristian Hveem, Bjørn Olav Åsvold, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada, Yoshinori Murakami, Bong-Jo Kim, Unnur Thorsteinsdottir, Kari Stefansson, Jifeng Zhang, YEugene Chen, Yuk-Lam Ho, Julie A. Lynch, Daniel J. Rader, Philip S. Tsao, Kyong-Mi Chang, Kelly Cho, Christopher J. O’Donnell, John M. Gaziano, Peter W. F. Wilson, Timothy M. Frayling, Joel N. Hirschhorn, Sekar Kathiresan, Karen L. Mohlke, Yan V. Sun, Andrew P. Morris, Michael Boehnke, Christopher D. Brown, Pradeep Natarajan, Panos Deloukas, Cristen J. Willer, Themistocles L. Assimes, and Gina M. Peloso
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Cholesterol ,Lipids ,Genetics ,Genome-wide association study ,GWAS ,Biology (General) ,QH301-705.5 ,QH426-470 - Abstract
Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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- 2022
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39. Association between physical activity and cancer risk among Chinese adults: a 10-year prospective study
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Jian Su, Yuchen Jiang, Xikang Fan, Ran Tao, Ming Wu, Yan Lu, Yujie Hua, Jianrong Jin, Yu Guo, Jun Lv, Pei Pei, Zhengming Chen, Liming Li, and Jinyi Zhou
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Physical activity ,Cancer ,Prospective cohort study ,Nutritional diseases. Deficiency diseases ,RC620-627 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background In China, the quantity of physical activity differs from that in Western countries. Substantial uncertainty remains about the relevance of physical activity for cancer subtypes among Chinese adults. Objective This study aimed to investigate the association between total daily physical activity and the incidence of common types of cancer. Methods A total of 53,269 participants aged 30–79 years were derived from the Wuzhong subcohort of the China Kadoorie Biobank study during 2004–2008. We included 52,938 cancer-free participants in the final analysis. Incident cancers were identified through linkage with the health insurance system and death registries. Cox proportional hazard models were introduced to assess the associations of total daily physical activity with the incidence of 6 common types of cancer. Results During a follow-up of 10.1 years, 3,674 cases of cancer were identified, including 794 (21.6%) from stomach cancer, 722 (19.7%) from lung cancer, 458 (12.5%) from colorectal cancer, 338 (9.2%) from liver cancer, 250 (6.8%) from breast cancer, and 231 (6.3%) from oesophageal cancer. Compared to the participants in the lowest quartile of physical activity levels, those in the highest quartile had an 11% lower risk for total cancer incidence (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.81–0.99), 25% lower risk for lung cancer incidence (HR: 0.75, 95% CI: 0.60–0.94), and 26% lower risk for colorectal cancer incidence (HR: 0.74, 95% CI: 0.55–1.00). There were significant interactions of physical activity with sex and smoking on total cancer (both P for interaction
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- 2022
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40. Maintaining healthy sleep patterns and frailty transitions: a prospective Chinese study
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Yunqing Zhu, Junning Fan, Jun Lv, Yu Guo, Pei Pei, Ling Yang, Yiping Chen, Huaidong Du, Feifei Li, Xiaoming Yang, Daniel Avery, Junshi Chen, Zhengming Chen, Canqing Yu, Liming Li, and on behalf of the China Kadoorie Biobank Collaborative Group
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Sleep patterns ,Frailty ,Prospective cohort study ,Medicine - Abstract
Abstract Background Little is known about the effects of maintaining healthy sleep patterns on frailty transitions. Methods Based on 23,847 Chinese adults aged 30–79 in a prospective cohort study, we examined the associations between sleep patterns and frailty transitions. Healthy sleep patterns included sleep duration at 7 or 8 h/d, without insomnia disorder, and no snoring. Participants who persisted with a healthy sleep pattern in both surveys were defined as maintaining a healthy sleep pattern and scored one point. We used 27 phenotypes to construct a frailty index and defined three statuses: robust, prefrail, and frail. Frailty transitions were defined as the change of frailty status between the 2 surveys: improved, worsened, and remained. Log-binomial regression was used to calculate the prevalence ratio (PR) to assess the effect of sleep patterns on frailty transitions. Results During a median follow-up of 8.0 years among 23,847 adults, 45.5% of robust participants, and 10.8% of prefrail participants worsened their frailty status, while 18.6% of prefrail participants improved. Among robust participants at baseline, individuals who maintained sleep duration of 7 or 8 h/ds, without insomnia disorder, and no-snoring were less likely to worsen their frailty status; the corresponding PRs (95% CIs) were 0.92 (0.89–0.96), 0.76 (0.74–0.77), and 0.85 (0.82–0.88), respectively. Similar results were observed among prefrail participants maintaining healthy sleep patterns. Maintaining healthy sleep duration and without snoring, also raised the probability of improving the frailty status; the corresponding PRs were 1.09 (1.00–1.18) and 1.42 (1.31–1.54), respectively. Besides, a dose-response relationship was observed between constantly healthy sleep scores and the risk of frailty transitions (P for trend
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- 2022
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41. External validation of models for predicting risk of colorectal cancer using the China Kadoorie Biobank
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Roxanna E. Abhari, Blake Thomson, Ling Yang, Iona Millwood, Yu Guo, Xiaoming Yang, Jun Lv, Daniel Avery, Pei Pei, Peng Wen, Canqing Yu, Yiping Chen, Junshi Chen, Liming Li, Zhengming Chen, and Christiana Kartsonaki
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Cancer epidemiology ,Colorectal cancer ,Risk prediction models ,External validation ,Medicine - Abstract
Abstract Background In China, colorectal cancer (CRC) incidence and mortality have been steadily increasing over the last decades. Risk models to predict incident CRC have been developed in various populations, but they have not been systematically externally validated in a Chinese population. This study aimed to assess the performance of risk scores in predicting CRC using the China Kadoorie Biobank (CKB), one of the largest and geographically diverse prospective cohort studies in China. Methods Nine models were externally validated in 512,415 participants in CKB and included 2976 cases of CRC. Model discrimination was assessed, overall and by sex, age, site, and geographic location, using the area under the receiver operating characteristic curve (AUC). Model discrimination of these nine models was compared to a model using age alone. Calibration was assessed for five models, and they were re-calibrated in CKB. Results The three models with the highest discrimination (Ma (Cox model) AUC 0.70 [95% CI 0.69–0.71]; Aleksandrova 0.70 [0.69–0.71]; Hong 0.69 [0.67–0.71]) included the variables age, smoking, and alcohol. These models performed significantly better than using a model based on age alone (AUC of 0.65 [95% CI 0.64–0.66]). Model discrimination was generally higher in younger participants, males, urban environments, and for colon cancer. The two models (Guo and Chen) developed in Chinese populations did not perform better than the others. Among the 10% of participants with the highest risk, the three best performing models identified 24–26% of participants that went on to develop CRC. Conclusions Several risk models based on easily obtainable demographic and modifiable lifestyle factor have good discrimination in a Chinese population. The three best performing models have a higher discrimination than using a model based on age alone.
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- 2022
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42. The role of NMR-based circulating metabolic biomarkers in development and risk prediction of new onset type 2 diabetes
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Fiona Bragg, Christiana Kartsonaki, Yu Guo, Michael Holmes, Huaidong Du, Canqing Yu, Pei Pei, Ling Yang, Donghui Jin, Yiping Chen, Dan Schmidt, Daniel Avery, Jun Lv, Junshi Chen, Robert Clarke, Michael R. Hill, Liming Li, Iona Y. Millwood, and Zhengming Chen
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Medicine ,Science - Abstract
Abstract Associations of circulating metabolic biomarkers with type 2 diabetes (T2D) and their added value for risk prediction are uncertain among Chinese adults. A case-cohort study included 882 T2D cases diagnosed during 8-years’ follow-up and a subcohort of 789 participants. NMR-metabolomic profiling quantified 225 plasma biomarkers in stored samples taken at recruitment into the study. Cox regression yielded adjusted hazard ratios (HRs) for T2D associated with individual biomarkers, with a set of biomarkers incorporated into an established T2D risk prediction model to assess improvement in discriminatory ability. Mean baseline BMI (SD) was higher in T2D cases than in the subcohort (25.7 [3.6] vs. 23.9 [3.6] kg/m2). Overall, 163 biomarkers were significantly and independently associated with T2D at false discovery rate (FDR) controlled p
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- 2022
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43. Association between frequency of dairy product consumption and hypertension: a cross-sectional study in Zhejiang Province, China
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Hao Wang, Lingli Chen, Yuan Cao, Kaixu Xie, Chunmei Wang, Pei Pei, Yu Guo, Fiona Bragg, Min Yu, Zhengming Chen, and Liming Li
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Hypertension ,Dairy products ,Cross-sectional study ,Nutrition. Foods and food supply ,TX341-641 ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background Hypertension, a well-known risk factor, contributes to millions of deaths from cardiovascular and renal diseases worldwide. However, evidence on the association between frequency of dairy product consumption and hypertension is inconsistent. Methods The data for the present study are from the Tongxiang baseline dataset of the China Kadoorie Biobank prospective study. A total of 53,916 participants aged 30–79 years were included in the final analysis. Multivariable logistic regression was utilized to evaluate the association of dairy product consumption with hypertension, and multiple linear regression was conducted to assess the association of dairy product consumption with systolic and diastolic blood pressure. Results Of the 53,916 participants, 2.6% reported consuming dairy products weekly, and 44.4% had prevalent hypertension. After adjusting for socio-demographic status, lifestyle factors, BMI, waist circumference, sleep duration and snoring, when compared with participants who never consumed dairy products, the odds ratios (95% CI) for hypertension among those consuming dairy products less than once per week, and ≥ 1 time per week were 0.85 (0.77–0.95) and 0.74 (0.65–0.84), respectively. The corresponding odds ratios (95% CI) for men were 0.85 (0.71–1.02) and 0.75 (0.61–0.92), respectively (P trend = 0.001), and for women were 0.88 (0.76–1.01) and 0.77 (0.65–0.91), respectively. (P trend
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- 2022
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44. TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma
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Tatiana Erazo, Chiara M. Evans, Daniel Zakheim, Eren L. Chu, Alice Yunsi Refermat, Zahra Asgari, Xuejing Yang, Mariana Da Silva Ferreira, Sanjoy Mehta, Marco Vincenzo Russo, Andrea Knezevic, Xi-Ping Zhang, Zhengming Chen, Myles Fennell, Ralph Garippa, Venkatraman Seshan, Elisa de Stanchina, Olena Barbash, Connie Lee Batlevi, Christina S. Leslie, Ari M. Melnick, Anas Younes, and Michael G. Kharas
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Science - Abstract
Abstract To identify drivers of sensitivity and resistance to Protein Arginine Methyltransferase 5 (PRMT5) inhibition, we perform a genome-wide CRISPR/Cas9 screen. We identify TP53 and RNA-binding protein MUSASHI2 (MSI2) as the top-ranked sensitizer and driver of resistance to specific PRMT5i, GSK-591, respectively. TP53 deletion and TP53 R248W mutation are biomarkers of resistance to GSK-591. PRMT5 expression correlates with MSI2 expression in lymphoma patients. MSI2 depletion and pharmacological inhibition using Ro 08-2750 (Ro) both synergize with GSK-591 to reduce cell growth. Ro reduces MSI2 binding to its global targets and dual treatment of Ro and PRMT5 inhibitors result in synergistic gene expression changes including cell cycle, P53 and MYC signatures. Dual MSI2 and PRMT5 inhibition further blocks c-MYC and BCL-2 translation. BCL-2 depletion or inhibition with venetoclax synergizes with a PRMT5 inhibitor by inducing reduced cell growth and apoptosis. Thus, we propose a therapeutic strategy in lymphoma that combines PRMT5 with MSI2 or BCL-2 inhibition.
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- 2022
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45. Conventional and genetic risk factors for chronic Hepatitis B virus infection in a community-based study of 0.5 million Chinese adults
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Elizabeth Hamilton, Ling Yang, Alexander J. Mentzer, Yu Guo, Yiping Chen, Jun Lv, Robert Fletcher, Neil Wright, Kuang Lin, Robin Walters, Christiana Kartsonaki, Yingcai Yang, Sushila Burgess, Sam Sansome, Liming Li, Iona Y. Millwood, and Zhengming Chen
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Medicine ,Science - Abstract
Abstract Despite universal vaccination of newborns, the prevalence of chronic hepatitis virus B (HBV) infection and the associated disease burden remain high among adults in China. We investigated risk factors for chronic HBV infection in a community-based study of 512,726 individuals aged 30–79 years recruited from ten diverse areas during 2004–2008. Multivariable logistic regression was used to estimate odds ratios (ORs) of hepatitis B surface antigen (HBsAg) positivity recorded at baseline by sociodemographic and lifestyle factors, and medical history. In a random subset (n = 69,898) we further assessed the association of 18 single nucleotide polymorphisms (SNPs) previously shown to be associated with HBsAg positivity and development of chronic liver disease (CLD) (1600 cases). Several factors showed strong associations with HBsAg positivity, particularly younger age (
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- 2022
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46. Epsilon toxin–producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege
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Yinghua Ma, David Sannino, Jennifer R. Linden, Sylvia Haigh, Baohua Zhao, John B. Grigg, Paul Zumbo, Friederike Dündar, Daniel Butler, Caterina P. Profaci, Kiel Telesford, Paige N. Winokur, Kareem R. Rumah, Susan A. Gauthier, Vincent A. Fischetti, Bruce A. McClane, Francisco A. Uzal, Lily Zexter, Michael Mazzucco, Richard Rudick, David Danko, Evan Balmuth, Nancy Nealon, Jai Perumal, Ulrike Kaunzner, Ilana L. Brito, Zhengming Chen, Jenny Z. Xiang, Doron Betel, Richard Daneman, Gregory F. Sonnenberg, Christopher E. Mason, and Timothy Vartanian
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Autoimmunity ,Microbiology ,Medicine - Abstract
Multiple sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specific causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection to show that people with MS were more likely to harbor and show a greater abundance of epsilon toxin–producing (ETX-producing) strains of C. perfringens within their gut microbiomes compared with individuals who are healthy controls (HCs). Isolates derived from patients with MS produced functional ETX and had a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, ETX can substitute for PTX. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE caused demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the neuroanatomical lesion distribution seen in MS. CNS endothelial cell transcriptional profiles revealed ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings suggest that ETX-producing C. perfringens strains are biologically plausible pathogens in MS that trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.
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- 2023
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47. Associations of muscle mass, strength, and quality with all-cause mortality in China: a population-based cohort study
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Man Wu, Yuxia Wei, Jun Lv, Yu Guo, Pei Pei, Jiachen Li, Huaidong Du, Ling Yang, Yiping Chen, Xiaohui Sun, Hua Zhang, Junshi Chen, Zhengming Chen, Canqing Yu, Liming Li, on behalf of the China Kadoorie Biobank Collaborative Group, and Jing Ni
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Medicine - Abstract
Abstract. Background. It remains unclear about the association of muscle mass, strength, and quality with death in the general Chinese population of diverse economical and geographical backgrounds. The present study aimed to comprehensively examine such associations across different regions in China. Methods. Based on the China Kadoorie Biobank study, the present study included 23,290 participants who were aged 38 to 88 years and had no prevalent cardiovascular diseases or cancer. Muscle mass and grip strength were measured using calibrated instruments. Arm muscle quality was defined as the ratio of grip strength to arm muscle mass. Low muscle mass, grip strength, and arm muscle quality were defined as the sex-specific lowest quintiles of muscle mass index, grip strength, and arm muscle quality, respectively. Cox proportional hazards models yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of all-cause mortality in relation to muscle mass, strength, and quality. Results. During a median follow-up of 3.98 years, 739 participants died. The HR (95% CI) of all-cause mortality risk was 1.28 (1.08–1.51) for low appendicular muscle mass index, 1.38 (1.16–1.62) for low total muscle mass index, 1.68 (1.41–2.00) for low grip strength, and 1.41 (1.20–1.66) for low arm muscle quality in models adjusted for sociodemographic characteristics, lifestyle factors, and medical histories. Conclusion. Low muscle mass, grip strength, and arm muscle quality are all associated with short-term increased risks of mortality, indicating the importance of maintaining normal muscle mass, strength, and quality for general Chinese adults.
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- 2022
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48. DNL-Net: deformed non-local neural network for blood vessel segmentation
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Jiajia Ni, Jianhuang Wu, Ahmed Elazab, Jing Tong, and Zhengming Chen
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Blood vessel segmentation ,Deep learning ,Non-local neural network ,Attention mechanisms ,Spatial pyramid pooling ,Medical technology ,R855-855.5 - Abstract
Abstract Background The non-local module has been primarily used in literature to capturing long-range dependencies. However, it suffers from prohibitive computational complexity and lacks the interactions among positions across the channels. Methods We present a deformed non-local neural network (DNL-Net) for medical image segmentation, which has two prominent components; deformed non-local module (DNL) and multi-scale feature fusion. The former optimizes the structure of the non-local block (NL), hence, reduces the problem of excessive computation and memory usage, significantly. The latter is derived from the attention mechanisms to fuse the features of different levels and improve the ability to exchange information across channels. In addition, we introduce a residual squeeze and excitation pyramid pooling (RSEP) module that is like spatial pyramid pooling to effectively resample the features at different scales and improve the network receptive field. Results The proposed method achieved 96.63% and 92.93% for Dice coefficient and mean intersection over union, respectively, on the intracranial blood vessel dataset. Also, DNL-Net attained 86.64%, 96.10%, and 98.37% for sensitivity, accuracy and area under receiver operation characteristic curve, respectively, on the DRIVE dataset. Conclusions The overall performance of DNL-Net outperforms other current state-of-the-art vessel segmentation methods, which indicates that the proposed network is more suitable for blood vessel segmentation, and is of great clinical significance.
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- 2022
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49. Dairy consumption and risks of total and site-specific cancers in Chinese adults: an 11-year prospective study of 0.5 million people
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Maria G. Kakkoura, Huaidong Du, Yu Guo, Canqing Yu, Ling Yang, Pei Pei, Yiping Chen, Sam Sansome, Wing Ching Chan, Xiaoming Yang, Lei Fan, Jun Lv, Junshi Chen, Liming Li, Timothy J. Key, Zhengming Chen, and on behalf of the China Kadoorie Biobank (CKB) Collaborative Group
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Cancer ,Dairy products ,Diet ,China ,Prospective cohort study ,Medicine - Abstract
Abstract Background Previous studies of primarily Western populations have reported contrasting associations of dairy consumption with certain cancers, including a positive association with prostate cancer and inverse associations with colorectal and premenopausal breast cancers. However, there are limited data from China where cancer rates and levels of dairy consumption differ importantly from those in Western populations. Methods The prospective China Kadoorie Biobank study recruited ~0.5 million adults from ten diverse (five urban, five rural) areas across China during 2004–2008. Consumption frequency of major food groups, including dairy products, was collected at baseline and subsequent resurveys, using a validated interviewer-administered laptop-based food frequency questionnaire. To quantify the linear association of dairy intake and cancer risk and to account for regression dilution bias, the mean usual consumption amount for each baseline group was estimated via combining the consumption level at both baseline and the second resurvey. During a mean follow-up of 10.8 (SD 2.0) years, 29,277 incident cancer cases were recorded among the 510,146 participants who were free of cancer at baseline. Cox regression analyses for incident cancers associated with usual dairy intake were stratified by age-at-risk, sex and region and adjusted for cancer family history, education, income, alcohol intake, smoking, physical activity, soy and fresh fruit intake, and body mass index. Results Overall, 20.4% of participants reported consuming dairy products (mainly milk) regularly (i.e. ≥1 day/week), with the estimated mean consumption of 80.8 g/day among regular consumers and of 37.9 g/day among all participants. There were significant positive associations of dairy consumption with risks of total and certain site-specific cancers, with adjusted HRs per 50 g/day usual consumption being 1.07 (95% CI 1.04–1.10), 1.12 (1.02–1.22), 1.19 (1.01–1.41) and 1.17 (1.07–1.29) for total cancer, liver cancer (n = 3191), female breast cancer (n = 2582) and lymphoma (n=915), respectively. However, the association with lymphoma was not statistically significant after correcting for multiple testing. No significant associations were observed for colorectal cancer (n = 3350, 1.08 [1.00–1.17]) or other site-specific cancers. Conclusion Among Chinese adults who had relatively lower dairy consumption than Western populations, higher dairy intake was associated with higher risks of liver cancer, female breast cancer and, possibly, lymphoma.
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- 2022
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50. Electronic Health Record–Based Absolute Risk Prediction Model for Esophageal Cancer in the Chinese Population: Model Development and External Validation
- Author
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Yuting Han, Xia Zhu, Yizhen Hu, Canqing Yu, Yu Guo, Dong Hang, Yuanjie Pang, Pei Pei, Hongxia Ma, Dianjianyi Sun, Ling Yang, Yiping Chen, Huaidong Du, Min Yu, Junshi Chen, Zhengming Chen, Dezheng Huo, Guangfu Jin, Jun Lv, Zhibin Hu, Hongbing Shen, and Liming Li
- Subjects
Public aspects of medicine ,RA1-1270 - Abstract
BackgroundChina has the largest burden of esophageal cancer (EC). Prediction models can be used to identify high-risk individuals for intensive lifestyle interventions and endoscopy screening. However, the current prediction models are limited by small sample size and a lack of external validation, and none of them can be embedded into the booming electronic health records (EHRs) in China. ObjectiveThis study aims to develop and validate absolute risk prediction models for EC in the Chinese population. In particular, we assessed whether models that contain only EHR-available predictors performed well. MethodsA prospective cohort recruiting 510,145 participants free of cancer from both high EC-risk and low EC-risk areas in China was used to develop EC models. Another prospective cohort of 18,441 participants was used for validation. A flexible parametric model was used to develop a 10-year absolute risk model by considering the competing risks (full model). The full model was then abbreviated by keeping only EHR-available predictors. We internally and externally validated the models by using the area under the receiver operating characteristic curve (AUC) and calibration plots and compared them based on classification measures. ResultsDuring a median of 11.1 years of follow-up, we observed 2550 EC incident cases. The models consisted of age, sex, regional EC-risk level (high-risk areas: 2 study regions; low-risk areas: 8 regions), education, family history of cancer (simple model), smoking, alcohol use, BMI (intermediate model), physical activity, hot tea consumption, and fresh fruit consumption (full model). The performance was only slightly compromised after the abbreviation. The simple and intermediate models showed good calibration and excellent discriminating ability with AUCs (95% CIs) of 0.822 (0.783-0.861) and 0.830 (0.792-0.867) in the external validation and 0.871 (0.858-0.884) and 0.879 (0.867-0.892) in the internal validation, respectively. ConclusionsThree nested 10-year EC absolute risk prediction models for Chinese adults aged 30-79 years were developed and validated, which may be particularly useful for populations in low EC-risk areas. Even the simple model with only 5 predictors available from EHRs had excellent discrimination and good calibration, indicating its potential for broader use in tailored EC prevention. The simple and intermediate models have the potential to be widely used for both primary and secondary prevention of EC.
- Published
- 2023
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