1,870 results on '"Kuang Lin"'
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2. 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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3. One-size-fits-all versus risk-category-based screening interval strategies for cardiovascular disease prevention in Chinese adults: a prospective cohort studyResearch in context
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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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4. 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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5. 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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6. 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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7. 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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8. 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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9. 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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10. 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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11. The contribution of Neanderthal introgression and natural selection to neurodegenerative diseases
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Zhongbo Chen, Regina H. Reynolds, Antonio F. Pardiñas, Sarah A. Gagliano Taliun, Wouter van Rheenen, Kuang Lin, Aleksey Shatunov, Emil K. Gustavsson, Isabella Fogh, Ashley R. Jones, Wim Robberecht, Philippe Corcia, Adriano Chiò, Pamela J. Shaw, Karen E. Morrison, Jan H. Veldink, Leonard H. van den Berg, Christopher E. Shaw, John F. Powell, Vincenzo Silani, John A. Hardy, Henry Houlden, Michael J. Owen, Martin R. Turner, Mina Ryten, and Ammar Al-Chalabi
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Neurodegenerative diseases ,Alzheimer's disease ,Parkinson's disease ,Amyotrophic lateral sclerosis ,Genetics ,Neanderthal ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how common variants associated with neurodegenerative disease risk are maintained by natural selection in the population despite their deleterious effects. In this study, we aimed to quantify the genome-wide contribution of Neanderthal introgression and positive selection to the heritability of complex neurodegenerative disorders to address these questions.We used stratified-linkage disequilibrium score regression to investigate the relationship between five SNP-based signatures of natural selection, reflecting different timepoints of evolution, and genome-wide associated variants of the three most prevalent neurodegenerative disorders: Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease.We found no evidence for enrichment of positively-selected SNPs in the heritability of Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, suggesting that common deleterious disease variants are unlikely to be maintained by positive selection. There was no enrichment of Neanderthal introgression in the SNP-heritability of these disorders, suggesting that Neanderthal admixture is unlikely to have contributed to disease risk.These findings provide insight into the origins of neurodegenerative disorders within the evolution of Homo sapiens and addresses a long-standing debate, showing that Neanderthal admixture is unlikely to have contributed to common genetic risk of neurodegeneration in anatomically-modern humans.
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- 2023
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12. Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts
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Ying Wang, Shinichi Namba, Esteban Lopera, Sini Kerminen, Kristin Tsuo, Kristi Läll, Masahiro Kanai, Wei Zhou, Kuan-Han Wu, Marie-Julie Favé, Laxmi Bhatta, Philip Awadalla, Ben Brumpton, Patrick Deelen, Kristian Hveem, Valeria Lo Faro, Reedik Mägi, Yoshinori Murakami, Serena Sanna, Jordan W. Smoller, Jasmina Uzunovic, Brooke N. Wolford, Cristen Willer, Eric R. Gamazon, Nancy J. Cox, Ida Surakka, Yukinori Okada, Alicia R. Martin, Jibril Hirbo, Kuan-Han H. Wu, Humaira Rasheed, Jibril B. Hirbo, Arjun Bhattacharya, Huiling Zhao, Esteban A. Lopera-Maya, Sinéad B. Chapman, Juha Karjalainen, Mitja Kurki, Maasha Mutaamba, Juulia J. Partanen, Ben M. Brumpton, Sameer Chavan, Tzu-Ting Chen, Michelle Daya, Yi Ding, Yen-Chen A. Feng, Christopher R. Gignoux, Sarah E. Graham, Whitney E. Hornsby, Nathan Ingold, Ruth Johnson, Triin Laisk, Kuang Lin, Jun Lv, Iona Y. Millwood, Priit Palta, Anita Pandit, Michael H. Preuss, Unnur Thorsteinsdottir, Matthew Zawistowski, Xue Zhong, Archie Campbell, Kristy Crooks, Geertruida H. de Bock, Nicholas J. Douville, Sarah Finer, Lars G. Fritsche, Christopher J. Griffiths, Yu Guo, Karen A. Hunt, Takahiro Konuma, Riccardo E. Marioni, Jansonius Nomdo, Snehal Patil, Nicholas Rafaels, Anne Richmond, Jonathan A. Shortt, Peter Straub, Ran Tao, Brett Vanderwerff, Kathleen C. Barnes, Marike Boezen, Zhengming Chen, Chia-Yen Chen, Judy Cho, George Davey Smith, Hilary K. Finucane, Lude Franke, Andrea Ganna, Tom R. Gaunt, Tian Ge, Hailiang Huang, Jennifer Huffman, Jukka T. Koskela, Clara Lajonchere, Matthew H. Law, Liming Li, Cecilia M. Lindgren, Ruth J.F. Loos, Stuart MacGregor, Koichi Matsuda, Catherine M. Olsen, David J. Porteous, Jordan A. Shavit, Harold Snieder, Richard C. Trembath, Judith M. Vonk, David Whiteman, Stephen J. Wicks, Cisca Wijmenga, John Wright, Jie Zheng, Xiang Zhou, Michael Boehnke, Daniel H. Geschwind, Caroline Hayward, Eimear E. Kenny, Yen-Feng Lin, Hilary C. Martin, Sarah E. Medland, Aarno V. Palotie, Bogdan Pasaniuc, Kari Stefansson, David A. van Heel, Robin G. Walters, Sebastian Zöllner, Cristen J. Willer, Mark J. Daly, and Benjamin M. Neale
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Global-Biobank Meta-analysis Initiative ,polygenic risk scores ,multi-ancestry genetic prediction ,accuracy heterogeneity ,Genetics ,QH426-470 ,Internal medicine ,RC31-1245 - Abstract
Summary: Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning and thresholding (P + T) and PRS-continuous shrinkage (CS). For both methods, using a European-based linkage disequilibrium (LD) reference panel resulted in comparable or higher prediction accuracy compared with several other non-European-based panels. PRS-CS overall outperformed the classic P + T method, especially for endpoints with higher SNP-based heritability. Notably, prediction accuracy is heterogeneous across endpoints, biobanks, and ancestries, especially for asthma, which has known variation in disease prevalence across populations. Overall, we provide lessons for PRS construction, evaluation, and interpretation using GBMI resources and highlight the importance of best practices for PRS in the biobank-scale genomics era.
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- 2023
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13. Improved prediction of fracture risk leveraging a genome-wide polygenic risk score
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Tianyuan Lu, Vincenzo Forgetta, Julyan Keller-Baruch, Maria Nethander, Derrick Bennett, Marie Forest, Sahir Bhatnagar, Robin G. Walters, Kuang Lin, Zhengming Chen, Liming Li, Magnus Karlsson, Dan Mellström, Eric Orwoll, Eugene V. McCloskey, John A. Kanis, William D. Leslie, Robert J. Clarke, Claes Ohlsson, Celia M. T. Greenwood, and J. Brent Richards
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Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction. Methods We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors. Results A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13–1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727–0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791–0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072. Conclusions We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.
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- 2021
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14. Genetic associations of adult height with risk of cardioembolic and other subtypes of ischemic stroke: A mendelian randomization study in multiple ancestries.
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Andrew B Linden, Robert Clarke, Imen Hammami, Jemma C Hopewell, Yu Guo, William N Whiteley, Kuang Lin, Iain Turnbull, Yiping Chen, Canqing Yu, Jun Lv, Alison Offer, Derrick Bennett, Robin G Walters, Liming Li, Zhengming Chen, Sarah Parish, and China Kadoorie Biobank Collaborative Group
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Medicine - Abstract
BackgroundTaller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke.Methods and findingsHeight-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p < 0.001) and stronger inverse associations with large-artery stroke (11% lower risk, OR 0.89 [0.84, 0.95], p < 0.001) and small-vessel stroke (13% lower risk, OR 0.87 [0.83, 0.92], p < 0.001). The findings in both UKB and CKB were directionally concordant with those observed in MEGASTROKE, but did not reach statistical significance: For presumed cardioembolic stroke, the ORs were 1.08 (95% CI 0.86, 1.35; p = 0.53) in UKB and 1.20 (0.77, 1.85; p = 0.43) in CKB; for other subtypes of ischemic stroke in UKB, the OR was 0.97 (95% CI 0.90, 1.05; p = 0.49); and for other nonlacunar stroke and lacunar stroke in CKB, the ORs were 0.89 (0.80, 1.00; p = 0.06) and 0.99 (0.88, 1.12; p = 0.85), respectively. In addition, genetically determined height was also positively associated with atrial fibrillation (available only in UKB), and with lean body mass and lung function, and inversely associated with low-density lipoprotein (LDL) cholesterol in both British and Chinese ancestries. Limitations of this study include potential bias from assortative mating or pleiotropic effects of genetic variants and incomplete generalizability of genetic instruments to different populations.ConclusionsThe findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.
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- 2022
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15. The genetic architecture of sporadic and multiple consecutive miscarriage
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Triin Laisk, Ana Luiza G. Soares, Teresa Ferreira, Jodie N. Painter, Jenny C. Censin, Samantha Laber, Jonas Bacelis, Chia-Yen Chen, Maarja Lepamets, Kuang Lin, Siyang Liu, Iona Y. Millwood, Avinash Ramu, Jennifer Southcombe, Marianne S. Andersen, Ling Yang, Christian M. Becker, Anders D. Børglum, Scott D. Gordon, Jonas Bybjerg-Grauholm, Øyvind Helgeland, David M. Hougaard, Xin Jin, Stefan Johansson, Julius Juodakis, Christiana Kartsonaki, Viktorija Kukushkina, Penelope A. Lind, Andres Metspalu, Grant W. Montgomery, Andrew P. Morris, Ole Mors, Preben B. Mortensen, Pål R. Njølstad, Merete Nordentoft, Dale R. Nyholt, Margaret Lippincott, Stephanie Seminara, Andres Salumets, Harold Snieder, Krina Zondervan, Thomas Werge, Zhengming Chen, Donald F. Conrad, Bo Jacobsson, Liming Li, Nicholas G. Martin, Benjamin M. Neale, Rasmus Nielsen, Robin G. Walters, Ingrid Granne, Sarah E. Medland, Reedik Mägi, Deborah A. Lawlor, and Cecilia M. Lindgren
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Science - Abstract
Miscarriage affects around 15% of clinically confirmed pregnancies. Here the authors carry out a large genome-wide association study for sporadic and multiple consecutive miscarriage and suggest links with placental biology.
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- 2020
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16. Application of Network Pharmacology to Explore the Mechanism of Yi Xin Tai Formula in Treating Heart Failure
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Wei Jia-Ming, Zhu Jun-Ping, Zhang Tong-Yu, Li Yu-Ying, Kuang Lin, Guo Zhi-Hua, and Li Ya
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Medicine ,Other systems of medicine ,RZ201-999 - Abstract
Objective: To explore the possible mechanism of Yi Xin Tai Formula (YXTF) in treating heart failure (HF) by network pharmacology method and to verify the related targets by western blotting. Methods: Using the traditional Chinese medicine systems pharmacology (TCMSP) database with its analysis platform for HF as a disease model, the active ingredients of YXTF were filtered according to the oral bioavailability (OB) and drug- likeness (DL), and the corresponding targets were predicted. The disease targets of HF were retrieved by Human Phenotype Ontology (HPO) database. Then, “YXTF compounds - Targets - HF” network was constructed in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, the network visualized through the Cytoscape software, and the key nodes of the network achieved according to Degree (D), Closeness Centrality (CC), and Betweenness Centrality (BC). Kyoto Encyclopedia of Genes and Genomes (KEGG) gene function enrichment analysis was carried out for the key nodes with the help of GATHER database platform. The rabbit model of HF was established by coarctation of the abdominal aorta and perfusion of propylthiouracil (PTU). The pathological changes and protein expression of transforming growth factor beta (TGF-β) protein were observed by western blotting. Results: “YXTF compounds - Targets - HF” network consisted of 403 nodes, 136 key nodes and 10 related KEGG pathways that included focal adhesions, cell cycles, mitogen-activated protein kinase (MAPK) signaling pathways, Toll-like receptor signaling pathways, Cytokine-cytokine receptor interactions, Gap junctions, adherens junctions, TGF-β signaling pathways, apoptosis and Wnt signaling pathways, respectively. The expression of TGF-β protein in myocardium decreased significantly. Conclusions: According to the network pharmacology, the treatment of YXTF for HF might be related to 10 metabolic pathways. The effects of the multicompound-multitarget-multi pathways and the synergistic effect drawn from the compounds that act as the monarch, minister, adjuvant, guide medicines were revealed through this study. Keywords: Yi Xin Tai Formula (YXTF), Heart failure (HF), Network pharmacology, Western blotting, TGF-β signal pathway
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- 2019
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17. Associations of autozygosity with a broad range of human phenotypes
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David W Clark, Yukinori Okada, Kristjan H S Moore, Dan Mason, Nicola Pirastu, Ilaria Gandin, Hannele Mattsson, Catriona L K Barnes, Kuang Lin, Jing Hua Zhao, Patrick Deelen, Rebecca Rohde, Claudia Schurmann, Xiuqing Guo, Franco Giulianini, Weihua Zhang, Carolina Medina-Gomez, Robert Karlsson, Yanchun Bao, Traci M Bartz, Clemens Baumbach, Ginevra Biino, Matthew J Bixley, Marco Brumat, Jin-Fang Chai, Tanguy Corre, Diana L Cousminer, Annelot M Dekker, David A Eccles, Kristel R van Eijk, Christian Fuchsberger, He Gao, Marine Germain, Scott D Gordon, Hugoline G de Haan, Sarah E Harris, Edith Hofer, Alicia Huerta-Chagoya, Catherine Igartua, Iris E Jansen, Yucheng Jia, Tim Kacprowski, Torgny Karlsson, Marcus E Kleber, Shengchao Alfred Li, Ruifang Li-Gao, Anubha Mahajan, Koichi Matsuda, Karina Meidtner, Weihua Meng, May E Montasser, Peter J van der Most, Matthias Munz, Teresa Nutile, Teemu Palviainen, Gauri Prasad, Rashmi B Prasad, Tallapragada Divya Sri Priyanka, Federica Rizzi, Erika Salvi, Bishwa R Sapkota, Daniel Shriner, Line Skotte, Melissa C Smart, Albert Vernon Smith, Ashley van der Spek, Cassandra N Spracklen, Rona J Strawbridge, Salman M Tajuddin, Stella Trompet, Constance Turman, Niek Verweij, Clara Viberti, Lihua Wang, Helen R Warren, Robyn E Wootton, Lisa R Yanek, Jie Yao, Noha A Yousri, Wei Zhao, Adebowale A Adeyemo, Saima Afaq, Carlos Alberto Aguilar-Salinas, Masato Akiyama, Matthew L Albert, Matthew A Allison, Maris Alver, Tin Aung, Fereidoun Azizi, Amy R Bentley, Heiner Boeing, Eric Boerwinkle, Judith B Borja, Gert J de Borst, Erwin P Bottinger, Linda Broer, Harry Campbell, Stephen Chanock, Miao-Li Chee, Guanjie Chen, Yii-Der I Chen, Zhengming Chen, Yen-Feng Chiu, Massimiliano Cocca, Francis S Collins, Maria Pina Concas, Janie Corley, Giovanni Cugliari, Rob M van Dam, Anna Damulina, Maryam S Daneshpour, Felix R Day, Graciela E Delgado, Klodian Dhana, Alexander S F Doney, Marcus Dörr, Ayo P Doumatey, Nduna Dzimiri, S Sunna Ebenesersdóttir, Joshua Elliott, Paul Elliott, Ralf Ewert, Janine F Felix, Krista Fischer, Barry I Freedman, Giorgia Girotto, Anuj Goel, Martin Gögele, Mark O Goodarzi, Mariaelisa Graff, Einat Granot-Hershkovitz, Francine Grodstein, Simonetta Guarrera, Daniel F Gudbjartsson, Kamran Guity, Bjarni Gunnarsson, Yu Guo, Saskia P Hagenaars, Christopher A Haiman, Avner Halevy, Tamara B Harris, Mehdi Hedayati, David A van Heel, Makoto Hirata, Imo Höfer, Chao Agnes Hsiung, Jinyan Huang, Yi-Jen Hung, M Arfan Ikram, Anuradha Jagadeesan, Pekka Jousilahti, Yoichiro Kamatani, Masahiro Kanai, Nicola D Kerrison, Thorsten Kessler, Kay-Tee Khaw, Chiea Chuen Khor, Dominique P V de Kleijn, Woon-Puay Koh, Ivana Kolcic, Peter Kraft, Bernhard K Krämer, Zoltán Kutalik, Johanna Kuusisto, Claudia Langenberg, Lenore J Launer, Deborah A Lawlor, I-Te Lee, Wen-Jane Lee, Markus M Lerch, Liming Li, Jianjun Liu, Marie Loh, Stephanie J London, Stephanie Loomis, Yingchang Lu, Jian’an Luan, Reedik Mägi, Ani W Manichaikul, Paolo Manunta, Gísli Másson, Nana Matoba, Xue W Mei, Christa Meisinger, Thomas Meitinger, Massimo Mezzavilla, Lili Milani, Iona Y Millwood, Yukihide Momozawa, Amy Moore, Pierre-Emmanuel Morange, Hortensia Moreno-Macías, Trevor A Mori, Alanna C Morrison, Taulant Muka, Yoshinori Murakami, Alison D Murray, Renée de Mutsert, Josyf C Mychaleckyj, Mike A Nalls, Matthias Nauck, Matt J Neville, Ilja M Nolte, Ken K Ong, Lorena Orozco, Sandosh Padmanabhan, Gunnar Pálsson, James S Pankow, Cristian Pattaro, Alison Pattie, Ozren Polasek, Neil Poulter, Peter P Pramstaller, Lluis Quintana-Murci, Katri Räikkönen, Sarju Ralhan, Dabeeru C Rao, Wouter van Rheenen, Stephen S Rich, Paul M Ridker, Cornelius A Rietveld, Antonietta Robino, Frank J A van Rooij, Daniela Ruggiero, Yasaman Saba, Charumathi Sabanayagam, Maria Sabater-Lleal, Cinzia Felicita Sala, Veikko Salomaa, Kevin Sandow, Helena Schmidt, Laura J Scott, William R Scott, Bahareh Sedaghati-Khayat, Bengt Sennblad, Jessica van Setten, Peter J Sever, Wayne H-H Sheu, Yuan Shi, Smeeta Shrestha, Sharvari Rahul Shukla, Jon K Sigurdsson, Timo Tonis Sikka, Jai Rup Singh, Blair H Smith, Alena Stančáková, Alice Stanton, John M Starr, Lilja Stefansdottir, Leon Straker, Patrick Sulem, Gardar Sveinbjornsson, Morris A Swertz, Adele M Taylor, Kent D Taylor, Natalie Terzikhan, Yih-Chung Tham, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Annika Tillander, Russell P Tracy, Teresa Tusié-Luna, Ioanna Tzoulaki, Simona Vaccargiu, Jagadish Vangipurapu, Jan H Veldink, Veronique Vitart, Uwe Völker, Eero Vuoksimaa, Salma M Wakil, Melanie Waldenberger, Gurpreet S Wander, Ya Xing Wang, Nicholas J Wareham, Sarah Wild, Chittaranjan S Yajnik, Jian-Min Yuan, Lingyao Zeng, Liang Zhang, Jie Zhou, Najaf Amin, Folkert W Asselbergs, Stephan J L Bakker, Diane M Becker, Benjamin Lehne, David A Bennett, Leonard H van den Berg, Sonja I Berndt, Dwaipayan Bharadwaj, Lawrence F Bielak, Murielle Bochud, Mike Boehnke, Claude Bouchard, Jonathan P Bradfield, Jennifer A Brody, Archie Campbell, Shai Carmi, Mark J Caulfield, David Cesarini, John C Chambers, Giriraj Ratan Chandak, Ching-Yu Cheng, Marina Ciullo, Marilyn Cornelis, Daniele Cusi, George Davey Smith, Ian J Deary, Rajkumar Dorajoo, Cornelia M van Duijn, David Ellinghaus, Jeanette Erdmann, Johan G Eriksson, Evangelos Evangelou, Michele K Evans, Jessica D Faul, Bjarke Feenstra, Mary Feitosa, Sylvain Foisy, Andre Franke, Yechiel Friedlander, Paolo Gasparini, Christian Gieger, Clicerio Gonzalez, Philippe Goyette, Struan F A Grant, Lyn R Griffiths, Leif Groop, Vilmundur Gudnason, Ulf Gyllensten, Hakon Hakonarson, Anders Hamsten, Pim van der Harst, Chew-Kiat Heng, Andrew A Hicks, Hagit Hochner, Heikki Huikuri, Steven C Hunt, Vincent W V Jaddoe, Philip L De Jager, Magnus Johannesson, Åsa Johansson, Jost B Jonas, J Wouter Jukema, Juhani Junttila, Jaakko Kaprio, Sharon L. R. Kardia, Fredrik Karpe, Meena Kumari, Markku Laakso, Sander W van der Laan, Jari Lahti, Matthias Laudes, Rodney A Lea, Wolfgang Lieb, Thomas Lumley, Nicholas G Martin, Winfried März, Giuseppe Matullo, Mark I McCarthy, Sarah E Medland, Tony R Merriman, Andres Metspalu, Brian F Meyer, Karen L Mohlke, Grant W Montgomery, Dennis Mook-Kanamori, Patricia B Munroe, Kari E North, Dale R Nyholt, Jeffery R O’connell, Carole Ober, Albertine J Oldehinkel, Walter Palmas, Colin Palmer, Gerard G Pasterkamp, Etienne Patin, Craig E Pennell, Louis Perusse, Patricia A Peyser, Mario Pirastu, Tinca J. C. Polderman, David J Porteous, Danielle Posthuma, Bruce M Psaty, John D Rioux, Fernando Rivadeneira, Charles Rotimi, Jerome I Rotter, Igor Rudan, Hester M Den Ruijter, Dharambir K Sanghera, Naveed Sattar, Reinhold Schmidt, Matthias B Schulze, Heribert Schunkert, Robert A Scott, Alan R Shuldiner, Xueling Sim, Neil Small, Jennifer A Smith, Nona Sotoodehnia, E-Shyong Tai, Alexander Teumer, Nicholas J Timpson, Daniela Toniolo, David-Alexandre Tregouet, Tiinamaija Tuomi, Peter Vollenweider, Carol A Wang, David R Weir, John B Whitfield, Cisca Wijmenga, Tien-Yin Wong, John Wright, Jingyun Yang, Lei Yu, Babette S Zemel, Alan B Zonderman, Markus Perola, Patrik K. E. Magnusson, André G Uitterlinden, Jaspal S Kooner, Daniel I Chasman, Ruth J. F. Loos, Nora Franceschini, Lude Franke, Chris S Haley, Caroline Hayward, Robin G Walters, John R. B. Perry, Tōnu Esko, Agnar Helgason, Kari Stefansson, Peter K Joshi, Michiaki Kubo, and James F Wilson
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Science - Abstract
Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.
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- 2019
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18. The transferability of lipid loci across African, Asian and European cohorts
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Karoline Kuchenbaecker, Nikita Telkar, Theresa Reiker, Robin G. Walters, Kuang Lin, Anders Eriksson, Deepti Gurdasani, Arthur Gilly, Lorraine Southam, Emmanouil Tsafantakis, Maria Karaleftheri, Janet Seeley, Anatoli Kamali, Gershim Asiki, Iona Y. Millwood, Michael Holmes, Huaidong Du, Yu Guo, Meena Kumari, George Dedoussis, Liming Li, Zhengming Chen, Manjinder S. Sandhu, Eleftheria Zeggini, and Understanding Society Scientific Group
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Science - Abstract
The majority of published GWAS was performed in European ancestry populations. Here, Kuchenbaecker et al., test to which extent lipid loci are shared and find that the major lipid loci are mostly transferrable between Europeans and Asians while there are notable exceptions for African populations.
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- 2019
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19. Mortality and recurrent vascular events after first incident stroke: a 9-year community-based study of 0·5 million Chinese adults
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Yiping Chen, DPhil, Neil Wright, PhD, Yu Guo, MSc, Iain Turnbull, MRCP, Christiana Kartsonaki, DPhil, Ling Yang, PhD, Zheng Bian, MSc, Pei Pei, BSc, Dongxia Pan, MBBS, Yidan Zhang, BSc, Haiqiang Qin, MD, Yilong Wang, ProfMD, Jun Lv, ProfPhD, Ming Liu, MD, Zilong Hao, MD, Yongjun Wang, ProfMD, Canqing Yu, PhD, Richard Peto, ProfFRS, Rory Collins, ProfFRS, Liming Li, ProfMPH, Robert Clarke, ProfFRCP, Zhengming Chen, ProfDPhil, Yiping Chen, Neil Wright, Yu Guo, Iain Turnbull, Christiana Kartsonaki, Ling Yang, Zheng Bian, Pei Pei, Dongxia Pan, Yidan Zhang, Haiqiang Qin, Yilong Wang, Jun Lv, Ming Liu, Zilong Hao, Yongjun Wang, Canqing Yu, Richard Peto, Rory Collins, Liming Li, Robert Clarke, Zhengming Chen, Junshi Chen, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Fiona Bragg, Yumei Chang, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Rene Kerosi, Garry Lancaster, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Paul Ryder, Sam Sansome, Dan Schmidt, Rajani Sohoni, Jenny Wang, Lin Wang, Xiaoming Yang, Xiao Han, Can Hou, Biao Jing, Chao Liu, Zengchang Pang, Ruqin Gao, Shanpeng Li, 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, Mingyuan Zeng, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Qinai Xu, Quan Kang, Ziyan Guo, Dan Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Zhifang Fu, 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, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Jian Lan, Yun Liu, Liuping Wei, Ningyu Chen, Ping Wang, Fanwen Meng, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Weiwei Zhou, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Xukui Zhang, Huifang Wu, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixu Xie, Lingli Chen, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Stroke is a leading cause of death and disability worldwide. Despite considerable improvements in diagnosis and treatment, little is known about the short-term and long-term prognosis after a first stroke in low-income and middle-income countries, including China. We aimed to assess the short-term and long-term risk of recurrent stroke and mortality after a first stroke for each of the major pathological stroke types. Methods: This population-based cohort study included adults aged 35–74 years without disability who were recruited to the China Kadoorie Biobank (CKB). A baseline survey was conducted in ten geographical areas (five urban, five rural) in China, and participants had clinical measurements recorded. Participants were followed up by monitoring death registries and by electronic linkage to health registries and health insurance claims databases, with follow-up until Jan 1, 2017. Participants were excluded from analyses if they had a previous history of stroke, transient ischaemic attack, or ischaemic heart disease at baseline. All incidences of fatal and non-fatal stroke during the study period were recorded by type (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and unspecified type). Primary outcome measures were 28-day mortality, recurrent stroke, major vascular events (recurrent stroke, myocardial infarction, or vascular death), vascular mortality, and all-cause mortality. Findings: Of 512 715 individuals in the CKB, 489 586 participants without previous ischaemic heart disease and stroke at recruitment were included, of whom 45 732 (42 073 [92%] confirmed by brain imaging) had a stroke during the study period. The mean age was 59·3 years (SD 9·8) for participants who had a stroke (54% women) and 50·8 years (10·3) for participants with no stroke (60% women). 36 588 (80%) of the incident cases of stroke were ischaemic stroke, 7440 (16%) were intracerebral haemorrhage, 702 (2%) were subarachnoid haemorrhage, and 1002 (2%) were an unspecified stroke type. 28-day mortality was 3% (95% CI 3–4) for ischaemic stroke, 47% (46–48)for intracerebral haemorrhage, 19% (17–22; 52% for rural areas and 32% for urban areas) subarachnoid haemorrhage, and 24% (22–27) for unspecified stroke. Among participants who survived stroke at 28 days, 41% (41–42) had recurrent stroke at 5 years (ischaemic stroke 41% [41–42], intracerebral haemorrhage 44% [42–46], subarachnoid haemorrhage 22% [18–27], unspecified stroke type 40% [35–44]) and mortality at 5 years was 17% ([17–18] ischaemic stroke 16% [15–16], intracerebral haemorrhage 28% [26–29], subarachnoid haemorrhage 16% [12–20], unspecified stroke type 15% [12–19]). After a first ischaemic stroke, 91% of recurrent strokes were also ischaemic stroke; after an intracerebral haemorrhage, 56% of recurrent strokes were intracerebral haemorrhage, and 41% of recurrent strokes were ischaemic stroke. Interpretation: After a first stroke, the risk of recurrence or death within 5 years was high among this population of Chinese adults. Urgent improvements to secondary prevention of stroke in China are needed to reduce these risks. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, National Natural Science Foundation of China. Copyright: © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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- 2020
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20. Cooking fuels and risk of all-cause and cardiopulmonary mortality in urban China: a prospective cohort study
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Kuai Yu, PhD, Jun Lv, PhD, Gaokun Qiu, PhD, Canqing Yu, PhD, Yu Guo, MSc, Zheng Bian, MSc, Ling Yang, PhD, Yiping Chen, DPhil, Chaolong Wang, ProfPhD, An Pan, ProfPhD, Liming Liang, ProfPhD, Frank B Hu, ProfPhD, Zhengming Chen, ProfDPhil, Liming Li, ProfMPH, Tangchun Wu, ProfPhD, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Ruth Boxall, Yumei Chang, Yiping Chen, Huaidong Du, Simon Gilbert, Alex Hacker, Mike Hill, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Ling Kong, Om Kurmi, Garry Lancaster, Sarah Lewington, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Zheng Bian, Xiao Han, Can Hou, Pei Pei, Chao Liu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shanpeng Li, 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, Mingyuan Zeng, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Qinai Xu, Quan Kang, Ziyan Guo, Dan Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Zhifang Fu, 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, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Jian Lan, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Ping Wang, Fanwen Meng, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Weiwei Zhou, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Xukui Zhang, Huifang Wu, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixu Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Qijun Gu, Yuelong Huang, Biyun Chen, Li Yin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Cooking practice has transitioned from use of solid fuels to use of clean fuels, with addition of better ventilation facilities. However, the change in mortality risk associated with such a transition remains unclear. Methods: The China Kadoorie Biobank (CKB) Study enrolled participants (aged 30–79 years) from ten areas across China; we chose to study participants from five urban areas where transition from use of solid fuels to clean fuels for cooking was prevalent. Participants who reported regular cooking (weekly or more frequently) at baseline were categorised as persistent clean fuel users, previous solid fuel users, or persistent solid fuel users, according to self-reported fuel use histories. All-cause and cardiopulmonary mortality were identified through linkage to China's Disease Surveillance Point system and local mortality records. Findings: Between June 24, 2004, and July 15, 2008, 226 186 participants living in five urban areas of China were enrolled in the CKB Study. Among 171 677 participants who reported cooking regularly (weekly or more frequently), 75 785 (44%) were persistent clean fuel users, 80 511 (47%) were previous solid fuel users, and 15 381 (9%) were persistent solid fuel users. During a mean of 9·8 (SD 1·7) years of follow-up, 10 831 deaths were documented, including 3819 cardiovascular deaths and 761 respiratory deaths. Compared with persistent clean fuel users, persistent solid fuel users had significantly higher risks of all-cause mortality (hazard ratio [HR] 1·19, 95% CI 1·10–1·28), cardiovascular mortality (1·24, 1·10–1·39), and respiratory mortality (1·43, 1·10–1·85). The excess risk of all-cause and cardiopulmonary mortality fell by more than 60% in 5 years after cessation of solid fuel use and continued to decrease afterwards. Use of ventilation was associated with lower all-cause mortality risk, even among persistent clean fuel users (HR 0·78, 0·69–0·89). Interpretation: Solid fuel use for cooking is associated with a higher risk of mortality, and cessation of solid fuel use cuts excess mortality risks swiftly and substantially within 5 years. Ventilation use also lowers the risk of mortality, even among people who persistently use clean fuels. It is of prime importance for both policy makers and the public to accelerate the transition from solid fuels to clean fuels and promote efficient ventilation to minimise further adverse health effects. Funding: National Natural Science Foundation of China, Wellcome Trust, and Kadoorie Charitable Foundation.
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- 2020
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21. Interethnic analyses of blood pressure loci in populations of East Asian and European descent
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Fumihiko Takeuchi, Masato Akiyama, Nana Matoba, Tomohiro Katsuya, Masahiro Nakatochi, Yasuharu Tabara, Akira Narita, Woei-Yuh Saw, Sanghoon Moon, Cassandra N. Spracklen, Jin-Fang Chai, Young-Jin Kim, Liang Zhang, Chaolong Wang, Huaixing Li, Honglan Li, Jer-Yuarn Wu, Rajkumar Dorajoo, Jovia L. Nierenberg, Ya Xing Wang, Jing He, Derrick A. Bennett, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Hiromi Rakugi, Eitaro Nakashima, Masato Isono, Matsuyuki Shirota, Atsushi Hozawa, Sahoko Ichihara, Tatsuaki Matsubara, Ken Yamamoto, Katsuhiko Kohara, Michiya Igase, Sohee Han, Penny Gordon-Larsen, Wei Huang, Nanette R. Lee, Linda S. Adair, Mi Yeong Hwang, Juyoung Lee, Miao Li Chee, Charumathi Sabanayagam, Wanting Zhao, Jianjun Liu, Dermot F. Reilly, Liang Sun, Shaofeng Huo, Todd L. Edwards, Jirong Long, Li-Ching Chang, Chien-Hsiun Chen, Jian-Min Yuan, Woon-Puay Koh, Yechiel Friedlander, Tanika N. Kelly, Wen Bin Wei, Liang Xu, Hui Cai, Yong-Bing Xiang, Kuang Lin, Robert Clarke, Robin G. Walters, Iona Y. Millwood, Liming Li, John C. Chambers, Jaspal S. Kooner, Paul Elliott, Pim van der Harst, The International Genomics of Blood Pressure (iGEN-BP) Consortium, Zhengming Chen, Makoto Sasaki, Xiao-Ou Shu, Jost B. Jonas, Jiang He, Chew-Kiat Heng, Yuan-Tsong Chen, Wei Zheng, Xu Lin, Yik-Ying Teo, E-Shyong Tai, Ching-Yu Cheng, Tien Yin Wong, Xueling Sim, Karen L. Mohlke, Masayuki Yamamoto, Bong-Jo Kim, Tetsuro Miki, Toru Nabika, Mitsuhiro Yokota, Yoichiro Kamatani, Michiaki Kubo, and Norihiro Kato
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Science - Abstract
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.
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- 2018
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22. Evidence for Dsg3 in regulating Src signaling by competing with it for binding to caveolin-1
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Hong Wan, Kuang Lin, Siu Man Tsang, and Jutamas Uttagomol
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Science (General) ,Q1-390 - Abstract
This data article contains extended, complementary analysis related to the research articles entitled “Desmoglein 3, via an interaction with E-cadherin, is associated with activation of Src” (Tsang et al., 2010) [1] and figures related to the review article entitled “Desmoglein 3: a help or a hindrance in cancer progression?” (Brown et al., 2014) [2]. We show here that both Src and caveolin-1 (Cav-1) associate with Dsg3 in a non-ionic detergent soluble pool and that modulation of Dsg3 levels inversely alters the expression of Src in the Cav-1 complex. Furthermore, immunofluorescence analysis revealed a reduced colocalization of Cav-1/total Src in cells with overexpression of Dsg3 compared to control cells. In support, the sequence analysis has identified a region within the carboxyl-terminus of human Dsg3 for a likelihood of binding to the scaffolding domain of Cav-1, the known Src binding site in Cav-1, and this region is highly conserved across most of 18 species as well as within desmoglein family members. Based on these findings, we propose a working model that Dsg3 activates Src through competing with its inactive form for binding to Cav-1, thus leading to release of Src followed by its auto-activation. Keywords: Desmoglein, Src signaling, Caveolin, Sequence alignment
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- 2016
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23. Adiposity and risk of ischaemic and haemorrhagic stroke in 0·5 million Chinese men and women: a prospective cohort study
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Zhengming Chen, ProfDPhil, Andri Iona, MSc, Sarah Parish, ProfDPhil, Yiping Chen, DPhil, Yu Guo, MSc, Fiona Bragg, DPhil, Ling Yang, PhD, Zheng Bian, MSc, Michael V Holmes, PhD, Sarah Lewington, DPhil, Ben Lacey, FFPH, Ruqin Gao, MSc, Fang Liu, MBBS, Zengzhi Zhang, MSc, Junshi Chen, ProfMD, Robin G Walters, PhD, Rory Collins, ProfFRS, Robert Clarke, ProfFRCP, Richard Peto, ProfFRS, Liming Li, ProfMPH, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Fiona Bragg, Yumei Chang, Yiping Chen, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Om Kurmi, Sarah Lewington, Garry Lancaster, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Zheng Bian, Ge Chen, Xiao Han, Can Hou, Pei Pei, Shuzhen Qu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Silu Lv, Junzheng Wang, Wei Hou, Jiyuan Yin, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren, Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang, Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang, Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Weiyuan Zhang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xuefeng Tang, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Yuelong Huang, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women. Methods: The China Kadoorie Biobank enrolled 512 891 adults aged 30–79 years from ten areas (five urban and five rural) during 2004–08. During a median 9 years (IQR 8–10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity. Findings: Mean baseline body-mass index (BMI) was 23·6 kg/m2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m2. Throughout the range examined (mean 17·1 kg/m2 [SD 0·9] to 31·7 kg/m2 [2·0]), each 5 kg/m2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28–1·33 per 5 kg/m2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 [1·24–1·26]). The HR for intracerebral haemorrhage (1·11 [1·07–1·16] per 5 kg/m2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 [1·46–1·50]). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 [1·03–1·07] per 5 kg/m2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 [0·70–0·77]). High adiposity (BMI >23 kg/m2) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of intracerebral haemorrhage). Interpretation: In Chinese adults, adiposity was strongly positively associated with ischaemic stroke, chiefly through its effect on blood pressure. For intracerebral haemorrhage, leanness, either per se or through some other factor (or factors), might increase risk, offsetting the protective effects of lower blood pressure. Funding: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, Chinese National Natural Science Foundation.
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- 2018
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24. Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study
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Ben Lacey, FFPH, Sarah Lewington, DPhil, Robert Clarke, ProfFRCP, Xiang Ling Kong, MSc, Yiping Chen, DPhil, Yu Guo, MSc, Ling Yang, PhD, Derrick Bennett, PhD, Fiona Bragg, DPhil, Zheng Bian, MSc, Shaojie Wang, MD, Hua Zhang, MD, Junshi Chen, ProfMD, Robin G Walters, PhD, Rory Collins, ProfFRS, Richard Peto, ProfFRS, Liming Li, ProfMPH, Zhengming Chen, ProfDPhil, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Fiona Bragg, Yumei Chang, Yiping Chen, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Andri Iona, Christiana Kartsonaki, Rene Kerosi, Om Kurmi, Sarah Lewington, Garry Lancaster, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Zheng Bian, Ge Chen, Xiao Han, Can Hou, Pei Pei, Shuzhen Qu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Silu Lv, Junzheng Wang, Wei Hou, Jiyuan Yin, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren, Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang, Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang, Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Weiyuan Zhang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xuefeng Tang, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Yuelong Huang, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. Methods: 512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. Findings: During a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (
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- 2018
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25. Smoking and smoking cessation in relation to risk of diabetes in Chinese men and women: a 9-year prospective study of 0·5 million people
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Xin Liu, PhD, Fiona Bragg, DPhil, Ling Yang, PhD, Christiana Kartsonaki, DPhil, Yu Guo, MSc, Huaidong Du, PhD, Zheng Bian, MSc, Yiping Chen, DPhil, Canqing Yu, PhD, Jun Lv, ProfPhD, Kang Wang, BSc, Hua Zhang, MSc, Junshi Chen, ProfMD, Robert Clarke, ProfFRCP, Rory Collins, ProfFRS, Richard Peto, ProfFRS, Liming Li, ProfMPH, Zhengming Chen, ProfDPhil, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Fiona Bragg, Yumei Chang, Yiping Chen, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Christiana Kartsonaki, Rene Kerosi, Garry Lancaster, Kuang Lin, John McDonnell, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Paul Ryder, Sam Sansome, Dan Schmidt, Rajani Sohoni, Becky Stevens, Iain Turnbull, Jenny Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Zheng Bian, Ge Chen, Xiao Han, Can Hou, Pei Pei, Shuzhen Qu, Yunlong Tan, Canqing Yu, Zengchang Pang, Ruqin Gao, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Silu Lv, Junzheng Wang, Wei Hou, Jiyuan Yin, Ge Jiang, Xue Zhou, Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren, Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang, Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang, Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang, Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Zhenzhu Tang, Naying Chen, Ying Huang, Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Weiyuan Zhang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xuefeng Tang, Guojin Luo, Jianguo Li, Xunfu Zhong, Jiaqiu Liu, Qiang Sun, Pengfei Ge, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan, Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Yijian Qian, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan, Yuelong Huang, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu, Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, and Zhe Qiu
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: In developed countries, smoking is associated with increased risk of diabetes. Little is known about the association in China, where cigarette consumption has increased (first in urban, then in rural areas) relatively recently. Moreover, uncertainty remains about the effect of smoking cessation on diabetes in China and elsewhere. We aimed to assess the associations of smoking and smoking cessation with risk of incident diabetes among Chinese adults. Methods: The prospective China Kadoorie Biobank enrolled 512 891 adults (59% women) aged 30–79 years during 2004–08 from ten diverse areas (five urban and five rural) across China. Participants were interviewed at study assessment clinics, underwent physical measurements, and had a non-fasting blood sample taken. Participants were separated into four categories according to smoking history: never-smokers, ever-regular smokers, ex-smokers, and occasional smokers. Incident diabetes cases were identified through linkage with diabetes surveillance systems, the national health insurance system, and death registries. All analyses were done separately in men and women and Cox regression was used to yield adjusted hazards ratios (HRs) for diabetes associated with smoking. Findings: 68% (n=134 975) of men ever smoked regularly compared with 3% (n=7811) of women. During 9 years' follow-up, 13 652 new-onset diabetes cases were recorded among 482 589 participants without previous diabetes. Among urban men, smokers had an adjusted HR of 1·18 (95% CI 1·12–1·25) for diabetes. HRs increased with younger age at first smoking regularly (1·12, 1·20, and 1·27 at ≥25 years, 20–24 years, and
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- 2018
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26. Predicting factors for acute encephalopathy in febrile seizure children with SARS-CoV-2 omicron variant: a retrospective study
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Tang, Ching-Min, Kuo, Cheng-Yen, Yen, Chen-Wei, Lin, Jainn-Jim, Hsieh, Yu-Chia, Hsia, Shao-Hsuan, Chan, Oi-Wa, Lee, En-Pei, Hung, Po-Cheng, Wang, Huei-Shyong, Lin, Kuang-Lin, and Chiu, Cheng-Hsun
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- 2024
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27. The role of Nocardia seriolae-induced autophagy in the development of chronic inflammation in the liver and the formation of granulomas in largemouth bass (Micropterus salmoides)
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Bai, Shang-Jie, Jian, Zheng-Ran, He, Sheng-Yu, Kuang, Lin-Feng, Zhou, Zheng-Yang, Lu, Chen-Wang, Zhong, Zhen-Dong, He, Jie, Xiong, Quan-Xin, Xiao, Shuang-Yan, Li, Peng-Fei, Liu, Ming-Zhu, Wang, Er-Long, Wang, Gao-Xue, Ling, Fei, Yu, Qing, and Liu, Tao
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- 2024
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28. The effects of exercise training on children with Epilepsy: A systematic review based on the ICF model
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Jeng, Shiau-Chian, Song, Cheng-Jhih, Lin, Kuang-Lin, and Liu, Wen-Yu
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- 2024
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29. Exploring the therapeutic potential of rutin through investigating its inhibitory mechanism on lactate dehydrogenase: Multi-spectral methods and computer simulation
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Ding, Pei, Yang, Kaiyu, Wang, Huixiao, Kuang, Lin, Gao, Linna, Luo, Jiaqing, and Tuo, Xun
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- 2024
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30. Mitochondrial damage and activation of NLRP3 induced by Yersinia ruckeri infection play an important role in the occurrence of diffuse acute inflammation of channel catfish (Ictalurus punctatus)
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Lu, Chen-Wang, He, Jie, Xiong, Quan-Xin, Zhong, Zhen-Dong, Yang, Bin, Lian, Sheng, Wang, Meng-Meng, Bai, Shang-Jie, Kuang, Lin-Feng, Zhou, Zheng-Yang, Jian, Zheng-Ran, Gao, Yuan-Chang, He, Sheng-Yu, Wang, Er-Long, Ling, Fei, Xiao, Shuang-Yan, Liu, Ming-Zhu, Li, Peng-Fei, Wang, Gao-Xue, Yu, Qing, and Liu, Tao
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- 2024
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31. Potential ecological risks of heavy metals and Cd accumulation characteristics of Suaeda salsa under different Cd input and water logging conditions in the Yellow River estuary, China
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Song, Hongli, Kuang, Lin, Wang, Lizhi, Yu, Wanni, Wu, Yuanzhi, An, Juan, and Wu, Xiyuan
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- 2023
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32. Electroencephalogram pattern predicting neurological outcomes of children with seizures secondary to abusive head trauma
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Chou, Cheng-Che, Hou, Ju-Yin, Chou, I-Jun, Lan, Shih-Yun, Kong, Shu-Sing, Huang, Man-Hsu, Weng, Yu-Chieh, Lin, Yi-Yu, Kuo, Cheng-Yen, Hsieh, Meng-Ying, Chou, Min-Liang, Hung, Po-Cheng, Wang, Huei-Shyong, Lin, Kuang-Lin, Wang, Yi-Shan, and Lin, Jainn-Jim
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- 2024
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33. Sleep problems during early and late infancy: Diverse impacts on child development trajectories across multiple domains
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Wang, Szu-Hua, Lin, Kuang-Lin, Chen, Chia-Ling, Chiou, Hawjeng, Chang, Chien-Ju, Chen, Po-Hsi, Wu, Ching-Yi, and Lin, Keh-chung
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- 2024
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34. Ferritin as an Effective Predictor of Neurological Outcomes in Children With Acute Necrotizing Encephalopathy
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Lee, En-Pei, Lin, Jainn-Jim, Chang, Han-Pi, Yen, Chen-Wei, Hsieh, Ming-Shun, Chan, Oi-Wa, Lin, Kuang-Lin, Su, Ya-Ting, Mu, Chun-Ting, and Hsia, Shao-Hsuan
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- 2024
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35. ETHER: Energy- and Cost-Efficient Framework for Seamless Connectivity over the Integrated Terrestrial and Non-terrestrial 6G Networks.
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Lechoslaw Tomaszewski, Robert Kolakowski, Agapi Mesodiakaki, Konstantinos Ntontin, Angelos Antonopoulos 0001, Nikolaos Pappas 0001, Marco Fiore, Mohammadreza Mosahebfard, Simon Watts, Philip Harris, Chih-Kuang Lin, Ana Rita Santiago, Fotis I. Lazarakis, and Symeon Chatzinotas
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- 2023
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36. Nocardia seriolae mediates granulomatous chronic inflammation of spleen in Micropterus salmoides through necroptosis
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Zhou, Zheng-Yang, He, Sheng-Yu, Lu, Chen-Wang, Bai, Shang-Jie, Kuang, Lin-Feng, Yang, Bin, Lian, Sheng, Jian, Zheng-Ran, Wang, Meng-Meng, Xiao, Shuang-Yan, Yu, Qing, Liu, Ming-Zhu, Li, Peng-Fei, Wang, Jun, Wang, Er-Long, Wang, Gao-Xue, Ling, Fei, and Liu, Tao
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- 2024
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37. Dravet-like syndrome with PCDH19 mutations in Taiwan ― A multicenter study
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Liu, Yi-Hsuan, Liang, Jao-Shwann, Chang, Ming-Yuh, Hung, Pi-Lien, Tsai, Meng-Han, Chou, I-Jun, Hou, Ju-Yin, Lee, Wang-Tso, and Lin, Kuang-Lin
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- 2024
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38. Risk factors of Omicron variant associated acute encephalitis/encephalopathy in children
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Huang, Chong-Wei, Lin, Jainn-Jim, Kuo, Chen-Yen, Lin, Kuang-Lin, Huang, Yhu-Chering, Chiu, Cheng-Hsun, Chen, Yi-Ching, Chen, Chih-Ho, and Hsieh, Yu-Chia
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- 2023
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39. Vectors for multi-color bimolecular fluorescence complementation to investigate protein-protein interactions in living plant cells
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Kuang Lin-Yun, Fang Mei-Jane, Lee Lan-Ying, and Gelvin Stanton B
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Plant culture ,SB1-1110 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background The investigation of protein-protein interactions is important for characterizing protein function. Bimolecular fluorescence complementation (BiFC) has recently gained interest as a relatively easy and inexpensive method to visualize protein-protein interactions in living cells. BiFC uses "split YFP" tags on proteins to detect interactions: If the tagged proteins interact, they may bring the two split fluorophore components together such that they can fold and reconstitute fluorescence. The sites of interaction can be monitored using epifluorescence or confocal microscopy. However, "conventional" BiFC can investigate interactions only between two proteins at a time. There are instances when one may wish to offer a particular "bait" protein to several "prey" proteins simultaneously. Preferential interaction of the bait protein with one of the prey proteins, or different sites of interaction between the bait protein and multiple prey proteins, may thus be observed. Results We have constructed a series of gene expression vectors, based upon the pSAT series of vectors, to facilitate the practice of multi-color BiFC. The bait protein is tagged with the C-terminal portion of CFP (cCFP), and prey proteins are tagged with the N-terminal portions of either Venus (nVenus) or Cerulean (nCerulean). Interaction of cCFP-tagged proteins with nVenus-tagged proteins generates yellow fluorescence, whereas interaction of cCFP-tagged proteins with nCerulean-tagged proteins generates blue fluorescence. Additional expression of mCherry indicates transfected cells and sub-cellular structures. Using this system, we have determined in both tobacco BY-2 protoplasts and in onion epidermal cells that Agrobacterium VirE2 protein interacts with the Arabidopsis nuclear transport adapter protein importin α-1 in the cytoplasm, whereas interaction of VirE2 with a different importin α isoform, importin α-4, occurs predominantly in the nucleus. Conclusion Multi-color BiFC is a useful technique to determine interactions simultaneously between a given" bait" protein and multiple "prey" proteins in living plant cells. The vectors we have constructed and tested will facilitate the study of protein-protein interactions in many different plant systems.
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- 2008
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40. Machine learning algorithms to automate differentiating cardiac amyloidosis from hypertrophic cardiomyopathy
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Wu, Zi-Wen, Zheng, Jin-Lei, Kuang, Lin, and Yan, Hui
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- 2023
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41. MRI of fatal course of acute hemorrhagic leukoencephalitis in a child with SARS-CoV-2 omicron BA 2.0 infection
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Wong, Alex Mun-Ching, Lin, Jainn-Jim, Hsia, Shao-Hsuan, and Lin, Kuang-Lin
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- 2023
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42. Investigation on the interaction of aromatic organophosphate flame retardants with human serum albumin via computer simulations, multispectroscopic techniques and cytotoxicity assay
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Ma, Xiulan, Kuang, Lin, Wang, Xiaowei, Zhang, Zihang, Chen, Chaolan, Ding, Pei, Chi, Baozhu, Xu, Junying, and Tuo, Xun
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- 2023
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43. A multispectral study and computer simulation on the interaction of pomalidomide with human serum albumin
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Zhou, Hui, Xiong, Ziyun, Ma, Xiulan, Dai, Lulu, Kuang, Lin, Deng, Ruihong, Lv, Xiaolan, and Tuo, Xun
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- 2023
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44. A Novel Method Combining Grayscale Images and Convolutional Neural Networks for Non-Intrusive Load Identifications.
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Men-Shen Tsai, Yuan-Hao Li, and Yen-Kuang Lin
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- 2022
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45. Incidence and prevalence of Tourette syndrome and chronic tic disorders in Taiwan: a nationwide population-based study
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Chou, I-Jun, Hung, Po-Cheng, Lin, Jainn-Jim, Hsieh, Meng-Ying, Wang, Yi-Shan, Kuo, Cheng-Yen, Kuo, Chang-Fu, Lin, Kuang-Lin, and Wang, Huei-Shyong
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- 2022
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46. Developmental and epileptic encephalopathies: Is prognosis related to different epileptic network dysfunctions?
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Lin, Jainn-Jim, Meletti, Stefano, Vaudano, Anna Elisabetta, and Lin, Kuang-Lin
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- 2022
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47. Divergent interpretations of child abuse in legal judgments: perspectives from clinicians and forensic experts.
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Tang, Ching-Min, Lou, Chen-Fang, Hsia, Shao-Hsuan, Liang, Kuang-Tsung, Chang, Wen, Lin, Jainn-Jim, Chan, Oi-Wa, Lin, Kuang-Lin, and Lee, En-Pei
- Abstract
Background: Child abuse in Taiwan is a major societal concern that severely affects the well-being of children. Despite the complexity in detecting abuse, reports of child abuse are increasing, evidenced by a rise in cases and heightened awareness. This study utilizes judicial judgments as a lens to understand the varied interpretations of child abuse by clinical and forensic experts and explores the broader epidemiological trends of such abuse within the declining youth population of Taiwan. Methods: We conducted a retrospective study by analyzing official court judgments on child abuse allegations judged from 2008 to 2022 from the online database of Judicial Yuan. Furthermore, the study analyzed demographic factors, injury patterns, and opinions from various experts. Results: The results reveal that severe criminal cases of child abuse predominantly involve biological fathers as the primary offenders and physical abuse as the most common form of maltreatment. Victims are typically aged less than 5 years, which frequently leads to an unfavorable prognosis. Analysis also highlights the TEN-4-FACESp acronym as a highly predictive indicator of child abuse and underscores the prevalence of abusive head trauma (AHT). Moreover, the findings emphasize ongoing disparities in opinions between forensic medical examiners and clinical physicians, especially in AHT cases, which potentially influences judicial decisions. Conclusions: In summary, the study reveals ongoing disagreements between forensic medical examiners and clinical physicians, especially in cases of AHT, which may impact judicial decisions. Promoting consensus through interdisciplinary collaboration and improved communication can aid in revealing the truth in child abuse cases. [ABSTRACT FROM AUTHOR]
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- 2024
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48. Situations and Risk Factors of Unplanned Extubation of Nasogastric Tubes in Inpatients: A Retrospective Study.
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Wen-Pei Chang and Yen-Kuang Lin
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- 2024
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49. Natural history in spinal muscular atrophy Type I in Taiwanese population: A longitudinal study
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Ou, Shan-Fu, Ho, Che-Sheng, Lee, Wang-Tso, Lin, Kuang-Lin, Jones, Cynthia C., and Jong, Yuh-Jyh
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- 2021
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50. Cardiac autonomic regulation following a 246-km mountain ultra-marathon: An observational study.
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I-Hsun Tsai, Wei-Fong Kao, Chorng-Kuang How, Li-Hua Li, Yen-Kuang Lin, Lu-Chih Kung, Yu-Hui Chiu, Ding-Kuo Chien, and Wen-Han Chang
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- 2024
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