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1. Thermal insulation and anti-vibration properties of MoSi2-based coating on mullite fiber insulation tiles

Author

He Dalong, Gao He, Jiao Fangkun, and Ou Dongbin

Subjects
Materials science, business.industry, Process Chemistry and Technology, Mullite, engineering.material, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Coating, Heat flux, Thermal insulation, Thermal radiation, Thermal, Materials Chemistry, Ceramics and Composites, engineering, Emissivity, Fiber, Composite material, business
Abstract

Thermal protection materials with excellent thermal insulation properties and high reliability are crucial for aerospace vehicle. Mullite fiber insulation tiles coated with MoSi2-borosilicate glass (MFIT@MoSi2) were prepared by a simple slurry method. Results shown that the surface temperature rapidly reached 1043.1 °C under the heat flux of 450 kW/m2, while the cold-surface remained at room temperature. The adjusting effects of MoSi2-based coating on the thermal response and transfer properties of MFIT were investigated systematically. Compared with MFIT, the surface and internal temperatures of MFIT@MoSi2 were obviously suppressed, due to the existence of MoSi2-based coating with high emissivity, which effectively enhanced the thermal radiation of the surfaces. Finally, the structural reliability under coupled environment of heating (q0 = 450 kW/m2) and random vibration with high magnitude (20–2000 Hz, Grms = 20 g) was also investigated. Destructive cracking and peeling of the coating were not observed, due to the excellent bonding strength between the coating and the substrate. The results provided an important basis for the potential application of insulation tiles with mullite fibers in aerospace vehicles and the design of lightweight thermal protection systems.

Published
2022

2. Overexpressed FAM166B Predicts Favorable Prognosis and Associated With Metabolic Pathways and Tumor Immune Infiltrates in BRCA

Author

Yi Zhou, Xuyu Cheng, Xiaoan Liu, Huiqin Zhu, Hongfei Zhang, and Gao He

Subjects
Metabolic pathway, Text mining, Immune system, business.industry, Cancer research, Medicine, Favorable prognosis, business
Abstract

Background: Breast cancer is one of the most common and lethal cancer worldwide. Though surgery, chemotherapy, endocrine therapy and immune therapy have boost patients' survival rate, to establish more molecular biomarkers that can detect the early metastasis and shed a light on breast cancer treatment still requires efforts. Based on previous studies, adipose tissue had a metabolic crosstalk in breast cancer. FAM166B is a protein-coding gene which was reported to be found in adipose tissues. Yet whether FAM166B has a role in breast cancer had not been determined.Methods: In this study, 1109 BRCA patients and 113 adjacent cancer samples and clinical characteristics data were downloaded from TCGA data portal, R software and Strawberry Perl were used for all pre-processing processes. Kaplan-Meier plotter, univariate and multivariate Cox analysis were used to investigate FAM166B potential in BRCA prognosis. GSEA was performed to investigate the biological function of FAM166B. Furthermore, TIMER was utilized to identify the association between FAM166B and tumor-infiltrating immune cells.Results: We found out increased FAM166B expression correlates with better prognosis in BRCA. By conducting Multivariate Cox analysis, we draw a conclusion that FAM166B could be an independent prognosis factor. Moreover, the GSEA revealed that FAM166B could possibly restrain the cell metabolism and glucose converting pathways. Also, a high expression of FAM166B was correlated with increased immune infiltration levels like CD4+ T cells and decreased macrophages, especially in luminal and basal breast cancers. Conclusion: Our study illustrated that FAM166B is an independent prognostic factor in BRCA. A high expression of FAM166B indicates a better prognosis of breast cancer patients and it may restrain the tumor cell metabolism and likely play a role in immune cell infiltration.

Published
2021

3. Energy Balance Analysis Simulated System for Remote Sensing Agile Satellite Based on MATLAB Function

Author

Yu Zhongjiang, Shuo Feng, Jianbo Du, Gao He, and Peng Kui

Subjects
Computer science, business.industry, media_common.quotation_subject, Process (computing), Energy balance, Power (physics), Satellite, MATLAB, Function (engineering), business, computer, Energy (signal processing), computer.programming_language, media_common, Remote sensing, Agile software development
Abstract

Remote sensing agile satellites have many load working modes and large changes in attitude during the period of on-orbit. In this case, the lighting conditions and load power conditions are often in a complex dynamic process. Traditional data tabular statistical methods bring great limitations to accurate analysis of satellite energy balance. This paper proposes a dynamic energy balance simulation system based on MATLAB function programming by dynamic parameter models, combined with a series of characteristics of remote sensing agile satellites, such as diverse mission modes and rapid maneuvers, etc. using functional modules for programming and simulation based analysis in specific scenarios. It could reflect the dynamic changes of energy balance accurately and clearly, the method is easy to program, friendly to interact and can dynamically reflect the energy utilization trend of the system, providing important reference for remote sensing agile satellite energy system.

Published
2020

4. Comparative analysis of locking plates versus hook plates in the treatment of Neer type II distal clavicle fractures

Author

Jun-Zu Hu, Peng Mao, Hong-Kai Wang, Li-Sheng Liang, Yu-Bin Su, and Ren-Gao He

Subjects
Adult, Male, Medicine (General), curative effect, Distal clavicle, Hook, Postoperative pain, clavicle hook plate, Biochemistry, Locking plate, Fracture Fixation, Internal, Fractures, Bone, 03 medical and health sciences, 0302 clinical medicine, R5-920, postoperative complications, Humans, Medicine, Distal clavicle fracture, 030212 general & internal medicine, Neer type II, Pain Measurement, Orthodontics, Curative effect, Pain, Postoperative, 030222 orthopedics, business.industry, Biochemistry (medical), Cell Biology, General Medicine, Middle Aged, Clavicle, Treatment Outcome, Female, postoperative pain, business, Bone Plates, Retrospective Clinical Research Report, locking plate, Follow-Up Studies
Abstract

Objective This study was performed to compare the clinical effects of locking plates (LPs) with those of hook plates (HPs) in the treatment of Neer type II distal clavicle fractures. Methods From August 2014 to April 2018, 64 patients with Neer type II distal clavicle fractures were treated in our department. The clinical effects were assessed with respect to the operation time, intraoperative blood loss, incision length, fracture healing, postoperative pain, postoperative complications, and postoperative shoulder joint function. Results There were no significant differences in the healing time, operation time, or intraoperative blood loss between the LP and HP groups. The incision length was significantly shorter in the LP than HP group, and the postoperative complication rate was significantly lower in the LP than HP group. The visual analog scale score, Constant–Murley score, and University of California Los Angeles score were significantly better in the LP than HP group. Conclusions Compared with HPs, the use of LPs involves a smaller incision in the treatment of Neer type II distal clavicle fractures and significantly reduces postoperative pain and complications. Therefore, priority can be given to the use of LPs in the treatment of Neer type II distal clavicle fractures.

Published
2020

6. Power System Transient Voltage Stability Assessment Based on Kernel Principal Component Analysis and DBN

Author

Gong Qing-wu, Liu Xu, Gao He, Qiao Hui, Chen Wenhui, Qian Wenxiao, Zheng Tingting, Zheng Bowen, Wu Liuchuang, Lu Jianqiang, Wang Bo, and Zhang Guoli

Subjects
Computer science, business.industry, 020209 energy, Deep learning, Feature vector, 02 engineering and technology, Filter (signal processing), Transient voltage suppressor, Kernel principal component analysis, Electric power system, Deep belief network, Control theory, 0202 electrical engineering, electronic engineering, information engineering, Redundancy (engineering), Artificial intelligence, business, Eigenvalues and eigenvectors
Abstract

Aiming at the transient voltage stability assessment of power system, this paper proposes a method based on kernel principal component analysis (KPCA) and deep belief network (DBN) for power system transient voltage stability assessment. Firstly, a set of 45-dimensional eigenvectors that can reflect the transient voltage stability of the power system is constructed. The feature vector set is reduced based on KPCA, the feature vector dimension and the filtering redundancy feature are reduced, then the dimensionality-reduced feature vector is input into the DBN network. The training process consists of pre-training and fine-tuning is performed to optimize the DBN grid structure parameters. The simulation results of the 10-machine 39-node in New England show that the method can reduce the dimension of input data, remove redundant features, reduce the error rate, and test time of transient stability assessment. It can accurately and quickly judge the steady state voltage state of the power system.

Published
2019

7. Research of CLL resonant DC-DC converter with wide input for battery system

Author

Qinglin Zhao, LiTao Qian, Gao He, Deyu Wang, and Zhe Zhang

Subjects
Physics, Battery system, business.industry, Wide input, 020208 electrical & electronic engineering, Electrical engineering, Buck–boost converter, Topology (electrical circuits), 02 engineering and technology, Modulation, 0202 electrical engineering, electronic engineering, information engineering, CLL resonant converter, Buck-Boost, Resonant converter, business, Dc dc converter, APWM, Power density, Voltage
Abstract

In this paper, a wide input voltage dc/dc CLL resonant converter is proposed. The presented converter topology consists a Buck-boost circuit and a CLL resonant network, and therefore the Buck-Boost circuit can be used to realize wide voltage input of the CLL resonant converter. In addition, the converter adopts APWM(Asymmetric Pulse-Width Modulation) constant frequency control, which makes the implement of CLL resonant converter easy. Moreover, the employed magnetic integration and switch integration technology can greatly improve power density as well as the cost. Finally, a prototype of 30-60V dc input and 25V/10A output (250W) is designed and the validity of the theoretical analysis and the validity of the theoretical analysis and design of proposed converter is verified by simulation.

Published
2019

8. Simulation and Analysis of Resonant Overvoltage of AC System at <tex>$\pm 800\mathrm{kV}$</tex> Converter Station based on EMTS/EMTPE

Author

Ren Zheng, Gao He, Zheng Bowen, Chen Xiaolu, and Lu Jianqiang

Subjects
Physics, business.industry, 020209 energy, Electrical engineering, 02 engineering and technology, Inductor, Transient voltage suppressor, law.invention, Inductance, Electric power system, Overvoltage, law, Power electronics, 0202 electrical engineering, electronic engineering, information engineering, RLC circuit, business, Transformer
Abstract

There are a large number of ac filters, reactors and other reactive compensation equipment in the $+800\mathbf{kV}$ converter station. Continuous switching of capacitive and inductive equipment may trigger resonant overvoltage. This article is based on power electronics and electromagnetic transient calculation program established $+800\mathbf{kV}$ ac system for electromagnetic transient model, to start debugging infill transformer and the ac system for filter when possible resonance overvoltage are analyzed in the simulation. The results show that the transient voltage during the start-up and commissioning of ac system of $+800\mathbf{kV}$ converter station is within the national standard limit and no resonant overvoltage is generated.

Published
2018

9. Study on Power Supply Reliability of Sending End Matching Power Access to Ultra-high Voltage AC and DC Hybrid Power Grid

Author

Liu Huibin, Gao He, Zheng Bowen, and Chen Xiaolu

Subjects
Power transmission, business.industry, Computer science, 020209 energy, Electrical engineering, 02 engineering and technology, Grid, computer.software_genre, Power (physics), Simulation software, Electric power system, Electricity generation, Hybrid system, 0202 electrical engineering, electronic engineering, information engineering, Hybrid power, business, computer
Abstract

With the continuous operation of ultra-high voltage (UHV) AC and DC power transmission and transformation projects in Inner Mongolia autonomous region, Inner Mongolia power grid has become a UHV AC and DC hybrid system. However, the development of AC and DC projects is not balanced, and the characteristics of “strong DC and weak AC” are obvious, It is bound to affect the safe and stable operation of UHV power grids, when sending end matching thermal power units connecting to UHV AC and DC hybrid power grid, the reliability of power supply is difficult to be guaranteed. Taking the sending end regional power grid of Xilinhot to Taizhou (Jiangsu Province) UHV DC transmission project (hereinafter referred to as Xitai DC) as the research object, by using Power System Analysis Software Package simulation software, this paper deeply analyzes the influence of high-power matching power supply on the safe and stable operation of the power grid after connecting to the UHV AC and DC hybrid power grid, and put forward the corresponding prevention and control measures.

Published
2018

10. Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes

Author

Rotroff, Daniel M., Pijut, Sonja S., Skylar W., Jack, John R., Havener, Tammy M., Pujol Onofre, Aurora, Schlüter, Agatha, Graf, Gregory A., Ginsberg, Henry N., Shah, Hetal S., Gao, He, Morieri, Mario-Luca, Doria, Alessandro, Mychaleckyi, Josyf C., Mcleod, Howard L., Buse, John B., Wagner, Michael J., Motsinger-Reif, Alison A., and ACCORD/ACCORDion Investigators

Subjects
0301 basic medicine, False discovery rate, Male, medicine.medical_specialty, Genome-wide association study, Type 2 diabetes, Disease, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Fenofibrate, Aldehyde Reductase, Internal medicine, Diabetes mellitus, Gene expression, medicine, Diabetes Mellitus, Animals, Humans, Pharmacology (medical), Smad3 Protein, Hypolipidemic Agents, Dyslipidemias, Pharmacology, Female, Gene Expression Profiling, Genome-Wide Association Study, Middle Aged, Pharmacogenomic Testing, Signal Transduction, beta Karyopherins, Diabetes Mellitus, Type 2, Lipid Metabolism, Diabetis, business.industry, Diabetes, nutritional and metabolic diseases, medicine.disease, 030104 developmental biology, Endocrinology, business, Dyslipidemia, Type 2, medicine.drug
Abstract

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10(−6)). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D.

Published
2018

11. Combined anatomic and physiologic scoring systems for predicting in-hospital mortality in ICU patients with severe trauma: A multicenter observational cohort study

Author

Huai-Jian Jin, Huaping Liang, Qian Wang, Bin Wang, Zhi-Gao He, Tao Chen, Lixing Tian, Wen Tao, Xiaoyuan Ma, and Jun-Yu Zhu

Subjects
acute physiology and chronic health evaluation ii, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, predictive value, Receiver operating characteristic, APACHE II, lcsh:RC955-962, business.industry, Glasgow Coma Scale, General Medicine, Confidence interval, Severe trauma, glasgow coma scale, Emergency medicine, new injury severity score, icu, Clinical endpoint, Medicine, Injury Severity Score, severe trauma, business, in-hospital mortality, Cohort study
Abstract

Objective: To evaluate the ability of new injury severity score (NISS), acute physiology and chronic health evaluation II (APACHE II), Glasgow coma scale (GCS), a combination of NISS and GCS, a combination of APACHE II and GCS, a combination of NISS and APACHE II to predict all-cause mortality of patients with severe trauma in mainland China. Methods: This was a multicenter observational cohort study conducted in the ICU of the Chonggang General Hospital, Daping Hospital of the Army Medical University and Affiliated Hospital of Zunyi Medical College from January 2012 to August 2016. The score of NISS, APACHE II, GCS, a combination of NISS and GCS, a combination of APACHE II and GCS, a combination of NISS and APACHE II were calculated based on data from the first 24 hours of ICU admission. Data were processed with Student’s t-test, chi-square test, and receiver operating characteristic (ROC) curve of six scoring systems. Calibration was assessed with the Hosmer-Lemeshow test. The primary endpoint was death from any cause during ICU stay. Results: A total of 852 and 238 patients with severe trauma were assigned to the derivation group and validation group, respectively. Area under the ROC curve (AUC) was 0.826 [95% confidence interval (CI)=0.794-0.855)] for NISS, 0.802 (95% CI=0.768-0.832) for APACHE II, 0.808 (95% CI=0.774-0.838) for NGCS, 0.859 (95% CI=0.829 -0.886) for NISS+NGCS, 0.864 (95% CI=0.835-0.890) for APACHE II +NGCS, 0.896 (95% CI=0.869-0.929) for NISS+APACHE II in the derivation cohort. Similarly, the score of NISS+APACHE II was also better than the other five scores in the validation cohort (AUC=0.782; 95% CI=0.725-0.833) and had a good calibration (P=0.41). Conclusions: Taking into account anatomical and physiological parameters completely, the combination of NISS and APACHE II performs better than NISS, APACHE II , NGCS, NISS+NGCS, APACHE II +NGCS for predicting mortality in ICU severe trauma patients. It is needful to develop models that contain various types of accessible predictors (demographic variables, injury cause/mechanism, physiological and anatomical variables, etc.) as comprehensive as possible.

Published
2019

12. Scenario: A New Paradigm for Replaying Day-to-Day Activities

Author

Yi Ding and Xin Gao He

Subjects
Engineering, Knowledge management, business.industry, Human–computer interaction, General Engineering, Information system, Information technology, Usability, Context (language use), Day to day, business
Abstract

Modern information technologies enable information systems to record the changing history of information units, and then play back such histories under users requests. This paper proposes a scenario paradigm equipped with a scenario-oriented approach to support the idea of replaying day-to-day activities. The proposed method attempts to organize related information and knowledge elements as a context (scenario) so that the history of daily activities can be recorded, and then be queried and replayed as a flow of information scenarios for a specified interval of time. Thats Your Life Information System (TYLI) is employed as an example in this paper for evaluating the usability of the scenario paradigm and the scenario-oriented approach.

Published
2013

14. Study on the Analysis Model of the Self-Centering Wall

Author

Xiao Bin Hu, Hao Xiang, Hui Gao He, and Wen Xia Li

Subjects
Engineering, Hysteresis, business.industry, Numerical analysis, General Medicine, Structural engineering, Residual, business, Finite element method, Displacement (vector), Damper, Connection (mathematics)
Abstract

The self-centering wall including both prestressed tendons and dampers is proposed in this paper, and the corresponding general finite element numerical analysis model, simplified numerical analysis model and theoretical analysis model were established respectively, focusing on how to simulate the prestressed tendons, dampers and the horizontal connection between the wall and the foundation. The numerical simulations of the self-centering wall subjected to reversal loading were performed using the above two numerical analysis models, and the results were compared to those obtained from theoretical analysis. It is indicated that the hysteresis curve of the self-centering wall under reversal loading exhibits flag shape and no residual displacement exists after the wall is unloaded completely. The numerical analysis results match well with those from theoretical analysis, which shows the two numerical analysis models proposed in this paper can be well used to capture the mechanical behavior of the self-centering wall.

Published
2013

15. A Cluster of Primary Pneumonic Plague Transmitted in a Truck Cab in a New Enzootic Focus in China

Author

Huiming Luo, Gao He, Xingqi Dong, Furong Li, Guang Zeng, Zhongjie Li, Zhizhong Song, Zhaohui Tong, Robert E. Fontaine, Hongtao Zhang, Zhujun Shao, Xu Xie, Tielong Yang, Zeyuan He, and Guangfa Wang

Subjects
Adult, Male, China, Pediatrics, medicine.medical_specialty, Yersinia pestis, medicine.disease_cause, Disease cluster, Bubonic plague, Young Adult, Bacterial Proteins, Virology, medicine, Humans, Blood culture, Seroconversion, Plague, medicine.diagnostic_test, biology, business.industry, Articles, Middle Aged, medicine.disease, biology.organism_classification, Antibodies, Bacterial, Influenza A virus subtype H5N1, Motor Vehicles, Pneumonia, Infectious Diseases, Enzootic, Female, Parasitology, business, human activities
Abstract

We investigated a cluster of five cases of severe pneumonia from one village in Yunnan Province, China. We searched for severe pneumonia in the village and hospitals. We interviewed patients and family members about exposures. We tested acute and convalescent sera for antigen and antibody of severe acute respiratory syndrome, avian influenza, and plague. The only common exposure of the five patients was riding together in the enclosed cab of a truck for 1.5 hours while taking the first patient to the hospital. Seroconversion to plague F1 antigen confirmed plague in three survivors. Unfamiliarity of clinicians with plague and lack of sputum examination, blood culture, or postmortem examination delayed the diagnosis. No plague cases occurred among family and village contacts and health care workers. High infectivity in this cluster was limited to a crowded, poorly ventilated truck.

Published
2013
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16. The Matrine Derivate MASM Prolongs Survival, Attenuates Inflammation, and Reduces Organ Injury in Murine Established Lethal Sepsis

Author

Jun-Ping Zhang, Weiheng Xu, Hong-Yuan Wu, Jing Xu, Yang Qi, Honggang Hu, Ke-Qi Wang, Yan Wang, Zhi-Gao He, Jian-Zhong Li, and Yinghua Li

Subjects
0301 basic medicine, MAPK/ERK pathway, Lipopolysaccharides, Male, Lipopolysaccharide, Inflammation, Pharmacology, Sepsis, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Alkaloids, Matrine, medicine, Immunology and Allergy, Animals, Immunologic Factors, Interleukin 6, Matrines, biology, business.industry, NF-κB, medicine.disease, Survival Analysis, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Infectious Diseases, RAW 264.7 Cells, chemistry, 030220 oncology & carcinogenesis, Immunology, biology.protein, Hepatic stellate cell, medicine.symptom, business, Quinolizines
Abstract

Background MASM, a novel derivative of matrine, has inhibitory effects on activation of macrophages, dendritic cells, and hepatic stellate cells and binds to ribosomal protein S5 (RPS5). This study was designed to evaluate the effect of MASM on murine-established lethal sepsis and its mechanisms. Methods Mouse peritoneal macrophages and RAW264.7 cells that were infected with recombinant lentiviruses encoding shRPS5 were incubated with lipopolysaccharide (LPS) in the absence or presence of MASM in vitro. Endotoxemia induced by LPS injection and sepsis induced by cecal ligation and puncture was followed by MASM treatment. Results MASM markedly attenuated LPS-induced release and messenger RNA expression of tumor necrosis factor α, interleukin 6, and NO/inducible NO synthase in murine peritoneal macrophages and RAW264.7 cells. Meanwhile, MASM inhibited LPS-induced activation of nuclear factor κB and MAPK pathways. Consistently, RPS5 suppressed LPS-induced inflammatory responses and at least in part mediated the antiinflammatory effect of MASM in vitro. Remarkably, delayed administration of MASM could significantly reduce mortality in mouse sepsis models, which was associated with the reduction in the inflammatory response, the attenuation in multiple organ injury, and the enhanced bacterial clearance. Conclusions MASM could be further explored for the treatments of sepsis, especially for administration later after the onset of sepsis.

Published
2016

17. An insulation condition assessment method of transformer based on set pair analysis and similarity clustering

Author

Gengshuo Liu, Ke-Jun Li, Gao He, Qiong Zhou, Hua Ge, and Ying Sun

Subjects
Engineering, business.industry, 020209 energy, Condition-based maintenance, 02 engineering and technology, Distribution transformer, Condition assessment, Maintenance engineering, Reliability engineering, law.invention, law, Assessment methods, 0202 electrical engineering, electronic engineering, information engineering, Cluster analysis, business, Transformer, Test data
Abstract

An insulation condition assessment method of the transformer is proposed in this paper. The set pair analysis and the expert evaluation method based on the set-valued statistics are adopted to assess insulation condition of the quantitative index and the qualitative index respectively according to the insulation condition assessment model of the transformer which is built. The subjective weight of evaluation index is determined by synthesizing the fuzzy analytic hierarchy process (FAHP) and the similarity clustering. The criteria importance through inter-criteria correlation (CRITIC) method is used to revise the subjective weight to the subjective and objective weight. The insulation condition of the transformer could be evaluated on the basis of the degradation value that is obtained with the weighted average method. The actual test data and inspection records of a distribution transformer are utilized to verify the assessment method and the numerical results testify that: we could evaluate the insulation condition of the transformer correctly and intuitively with the assessment method proposed in this paper, and considering authority of experts and objectivity of weights could give a more reasonable assessment result than ignoring them. The research in this paper could provide a feasible reference for the insulation condition assessment and technical support for the condition based maintenance of the transformer.

Published
2016

18. Analysis of BRAFV600E Mutation and Persistence of Papillary Thyroid Cancer after Total Thyroidectomy and Routine Central Neck Dissection

Author

Lin-gao He, Ten-fei Xing, Qian-qian Han, Feng liu, Feng Ye, Rixiang Gong, Wei Gao, Libo Yang, Zhihui Li, and Jingqiang Zhu

Subjects
medicine.medical_specialty, Pathology, endocrine system diseases, business.industry, medicine.medical_treatment, 030209 endocrinology & metabolism, Neck dissection, medicine.disease, Omics, Gastroenterology, Papillary thyroid cancer, Persistence (computer science), 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Internal medicine, Mutation (genetic algorithm), Medicine, Thyroglobulin, business, Lymph node, Thyroid cancer
Abstract

Purpose The aim of this study is to investigate the predictive value of BRAF V600E mutation for the persistence of papillary thyroid cancer (PTC) after total thyroidectomy and routine central neck dissection. Patients and Methods We collect the clinicopathological data of 288 PTC patients with total thyroidectomy (TT) and routine central neck dissection (CND), and analyzed the relationship between BRAFV600E mutation status and the rate of elevated non-stimulated thyroglobulin (NSTg) value. And we also collect the clinicopathological data of 370 PTC patients who needed radio iodine ablation(RIA) after TT and routine CND, and analyzed the relationship between BRAFV600E mutation status and the rate of elevated stimulated Tg (STg)value before RIA. The clinicopathological data included gender, age at diagnosis, multifocality, bilaterality, tumor size, extrathyroidal invasion, and lymph node status of these patients. All the patents were diagnosis as PTC before operation by the combination with ultrasonograph and FNA (fine needle asperation). Results BRAFV600E mutation is not associated with the elevated rate of elevated Tg value after TT and routine CND. Conclusions BRAF V600E mutation is not an independent predictive factor for the persistence of papillary thyroid cancer (PTC) after TT and routine CND.

Published
2016

19. Development for the Optimization Technique of the Coiling Tension in Degreasing Unit

Author

Qing Tian Zhou, Xiao Dong Shi, Zhen Hua Bai, Gao He, Dong Dong Zhang, and Hong Xin Si

Subjects
Engineering, Engineering drawing, Degreasing, business.industry, Electromagnetic coil, Mechanical engineering, General Medicine, Quadratic function, Production efficiency, business, Internal stress
Abstract

As to the production of degreasing unit, fully integrated with the equipment and technological features of the line, the approach for the setting of coiling tension was changed, which was mainly tabular method in the past. Under the new idea, the degreasing process was closely integrated with the bell-type annealing for the first time. Then, to minimize the severity of stick breaks was set as the objective function, and no loose coil and no heart-shaped coil is took as the constraint condition. On these bases, a new comprehensive optimization model for the setting of coiling tension in degreasing unit was put forward. The relation between coiling tension and coil radius was obtained, which was a quadratic curve. This simple and practical technology can make the distribution of internal stress of coil more reasonable, and reduce the incidence of stick breaks, loose coil and heart-shaped coil defects effectively and improve production efficiency, quality and the metal yield.

Published
2011

20. Three Dimensional Reconstruction System Based on Laser Radar

Author

Cheng Jun Tian, Bing Gao He, Zhi Yong An, and Lijuan Li

Subjects
Engineering, Radar engineering details, Lidar, Pulse-Doppler radar, business.industry, Radar imaging, Measuring principle, General Engineering, Range (statistics), Point cloud, business, Remote sensing, Geometric data analysis
Abstract

With the development of manufacturing, obtaining 3D data of objects surface effectively and precisely has been important. In this paper, laser radar is selected to gain 3D geometric data by comparing the current digital measurement techniques, and the measurement principle of laser radar is discussed in detail. For obtaining the whole surface points cloud of work piece and reducing the error of station moving, the mathematical model of station moving is established. This paper also analyzes the characteristics of points cloud data collected using laser radar, estimates the normals of scattered points with PCA method. Finally, the 3D surface of work piece is reconstructed using radial basis function interpolation.This system has the advantages of fast measurement speed, large measurement range and high degree automation.Because laser radar uses optical non-contact measurement mode, so there are no special requirements of the object surface.

Published
2010

21. Treatment with incomplete Freund's adjuvant and Listeria monocytogenes delays diabetes via an interleukin-17-secretion-independent pathway

Author

Zhi‑Gao He and Hai‑Ping Wang

Subjects
Cancer Research, Innate immune system, business.industry, medicine.medical_treatment, Interleukin, chemical and pharmacologic phenomena, General Medicine, Nod, Articles, Natural killer T cell, Immunology and Microbiology (miscellaneous), Immunology, parasitic diseases, medicine, Cytotoxic T cell, Interleukin 17, business, Adjuvant, NOD mice
Abstract

Non-obese diabetes (NOD) mice are widely used as an animal model in studies of type I diabetes (TID). Treatment with complete Freund's adjuvant (CFA) in pro-diabetic NOD mice is known to inhibit disease progression by activating CD1d-specific natural killer (NK) T cells and inducing interleukin (IL)-17 secretion in innate immune cells. The aim of the present study was to examine the effect of incomplete Freund's adjuvant (IFA) and L. monocytogenes treatment on the development of TID in NOD mice. This combined treatment of IFA and L. monocytogenes, a microbe that infects the liver and is primarily combatted by NK and cytotoxic T lymphocytes, was applied to mimic CFA treatment in pro-diabetic NOD mice. The combined IFA + L. monocytogenes treatment effectively delayed TID development in the NOD mice. In contrast to CFA, the IFA + L. monocytogenes treatment did not induce T cells or innate immune cells to secrete IL-17. However, increased levels of regulatory T cells were detected. Furthermore, IFA + L. monocytogenes mice exhibited higher levels of IgG2a, although no notable T helper 1 cell response was observed when compared with the CFA or IFA control treated mice. Therefore, combined IFA + L. monocytogenes treatment was shown to delay TID development in NOD mice via a novel mechanism, which was independent from the secretion of IL-17 by CFA-activated NKT cells.

Published
2015

22. Treatment of prostatic hyperplasia by plum-blossom-magnet-needle synthetic therapy: A report of 149 cases

Author

Liu Qing-guo and Gao He-yu

Subjects
Terazosin Hydrochloride, Dry needling, medicine.medical_specialty, Massage, business.industry, Therapeutic effect, Significant difference, Urology, Hyperplasia, medicine.disease, Surgery, medicine.anatomical_structure, Complementary and alternative medicine, Prostate, medicine, Acupuncture, business
Abstract

Purpose: To observe the therapeutic effect of plum-blossom-magnet-needle synthetic therapy on benign prostatic hyperplasia (BPH). Method: 219 cases of BPH patients were randomly divided into two groups. There were 149 cases in treatment group, which treated by pressing, needling with plum-blossom-magnet-needle and putting effect-increasing pads on Prostate Reflex Area, bilateral Zhongliao (BL 32), Neck 1, Neck 7, Mingmen (GV 4) and Yongquan (KI 1). There were 70 cases in control group, which treated by orally taken Terazosin Hydrochloride (Gaoteling) tablets, 2 mg/time, twice a day. The therapeutic course was 4 weeks. After one therapeutic course, the therapeutic effect was evaluated. Results: The marked effect rate was 63.3% and total effective rate was 91.8%; in the control group, there were no markedly effective cases and the total effective rate was 72.7%. There was a significant difference between two groups (P

Published
2005

23. Application of the Cross-Bridge Microvascular Anastomosis When No Recipient Vessels Are Available for Anastomosis: 85 Cases

Author

Bing-fang Zeng, He-gao He, Shen Yu, Zhong-jia Yu, Pei-zhu Jiang, Shu-ping Sui, and Yu-chi Huang

Subjects
Adult, Male, Microsurgery, medicine.medical_specialty, Soft Tissue Injuries, Adolescent, Anastomosis, Surgical Flaps, Ilium, Surgical anastomosis, medicine.artery, medicine, Humans, Radial artery, Child, Muscle, Skeletal, Cephalic vein, business.industry, Anastomosis, Surgical, Great saphenous vein, Middle Aged, Plastic Surgery Procedures, musculoskeletal system, Roux-en-Y anastomosis, Surgery, Posterior tibial artery, Fibula, Child, Preschool, Anterior tibial artery, Female, business, Leg Injuries
Abstract

The purpose of this article is to introduce the results of free tissue transfers using the technique of the cross-bridge microvascular anastomosis when the recipient lacks suitable vessels for anastomosis. Between May of 1982 and June of 2002, a series of 85 patients underwent this procedure. The transferred tissues were the free latissimus dorsi myocutaneous flap, the free vascularized fibula, the free fibular osteocutaneous flap, and the free iliac osteocutaneous flap, alone or in combination. The donor vessels were the anterior tibial artery and great saphenous vein, the posterior tibial artery and its venae comitantes, and the radial artery and cephalic vein. Good results were achieved. The success rate reached 95.29 percent. The authors believe this procedure can be performed in the event of serious tissue defect where the vessels are unsuitable for anastomosis.

Published
2004

24. The study on China's composition of high-tech products export trade

Author

Gao He and Wang Yan

Subjects
International market, Incentive, business.industry, Innovation management, Economics, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Profitability index, International trade, business, China, Trade barrier, High tech, Export trade
Abstract

Since 21st century, China's high-tech products foreign trade has got rapid development. As the matter of the factors of long-term dependence on foreign technologies, low intensity of R&D and lacking of the incentives of innovation lead to many problems, which are lower level of products, poor profitability, large risks and closer dependence on foreign-owned enterprises. China should adopt countermeasures, such as increasing efficiency of introduced technologies, augmenting R&D intensities, enhancing the native enterprises' ability to export, widening the international market for exports, to optimize the composition of high-tech products export trade.

Published
2013

25. The study on the Sino-Korean trade relations in the post-financial crisis period

Author

Gao He and Wang Yan

Subjects
Economic integration, Commercial policy, Globalization, Bilateral trade, International free trade agreement, business.industry, Economics, Trade in services, International economics, International trade, Trade barrier, business, Free trade
Abstract

China and Korea are two important economies in Asia, even in the world. Recently, the Sino-Korean economic and trade relations showed a momentum of good development overall, the two economies are major trade partners each other with higher trade dependence. However, there are still such problems as bilateral trade imbalance, frequent trade frictions, keen market competition. As the influence of financial crisis weakens, the governments of two economies should carry out intergovernmental exchange and cooperation, promote the building of Sino-Korea FTA, reduce the trade barriers, optimize industrial structures, increase the bilateral investment, promote the balanced development of bilateral trade, enhance the growth of trade in services and technology trade, so that seek for new growth point in bilateral trade and promote steady development of the bilateral trade relations.

Published
2013

26. The study on the international competitiveness of China's foreign trade in service

Author

Gao He and Wang Yan

Subjects
Commercial policy, business.industry, Service economy, media_common.quotation_subject, ComputingMilieux_LEGALASPECTSOFCOMPUTING, International trade, International trade and water, International economics, Fair trade, Service (economics), Economics, Trade barrier, business, Tertiary sector of the economy, International finance, media_common
Abstract

After Reform and Opening-up, China takes part in the international trade actively, especially the foreign trade in service develops dramatically with the expansion of the trade scale, the various trade modes and optimizing of trade structure. But the analysis of the international competitiveness of it shows that China's foreign trade in service is short of international competiveness obviously, and the structure of the service industry is unreasonable. Thus, to make the development strategy of the service industry, to establish large and powerful service enterprises, to build international famous service brand and to promote the service industry to `go-out' are the selectable measures of strengthening the competitiveness of China's foreign trade in service.

Published
2013

27. The comparative analysis of Sino-Japan trade in creative goods

Author

Wang Yan and Gao He

Subjects
business.industry, media_common.quotation_subject, Innovation management, International trade, Creativity, ComputingMilieux_GENERAL, Market research, Goods and services, International free trade agreement, Economics, business, China, Trade barrier, Free trade, ComputingMilieux_MISCELLANEOUS, media_common
Abstract

China and Japan are major traders in creative goods in Asia even in all over the world, while there are many differences in the development of trade in creative goods. It shows that through comparative analysis China has stronger advantage in trade volume, but still has larger gap in many aspects, such as relative lag in nation's strategy, weaker creativity and cultural artistry within products, too lower ability of creating trade value, and so on. Thus, China should pay more attention to formulate the strategy in developing creative industry, carry out some statics of strengthening the creativity of goods and marketing the goods, and promote further the development of China's foreign trade in creative goods.

Published
2013

28. Calibration of camera-with-filter using projected features

Author

Tan Haishu, Gao He, Li Yanping, and Zhou Fuqiang

Subjects
Filter (video), Camera auto-calibration, business.industry, Computer science, Calibration, Computer vision, Artificial intelligence, business, Structured-light 3D scanner
Published
2012

30. Peripheral Leukocytapheresis Attenuates Acute Lung Injury Induced by Lipopolysaccharide In Vivo

Author

Jing He, Jian Huang, Fang-xiang Chen, Shun-gang Zhou, Xian-kai Huang, and Zhi-gao He

Subjects
Lipopolysaccharides, Male, ARDS, Lipopolysaccharide, Article Subject, Acute Lung Injury, Immunology, Apoptosis, Lung injury, Models, Biological, Random Allocation, chemistry.chemical_compound, Dogs, Parenchyma, Leukocytes, medicine, lcsh:Pathology, Animals, Leukapheresis, Lung, Respiratory Distress Syndrome, biology, business.industry, Elastase, NF-kappa B, Cell Biology, respiratory system, medicine.disease, Endotoxemia, respiratory tract diseases, medicine.anatomical_structure, chemistry, Neutrophil elastase, biology.protein, Arterial blood, Blood Gas Analysis, Leukocyte Elastase, business, Bronchoalveolar Lavage Fluid, Research Article, lcsh:RB1-214
Abstract

The mortality of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains high and efforts for prevention and treatments have shown little improvement over the past decades. The present study investigated the efficacy and mechanism of leukocytapheresis (LCAP) to partially eliminate peripheral neutrophils and attenuate lipopolysaccharide (LPS)-induced lung injury in dogs. A total of 24 healthy male mongrel dogs were enrolled and randomly divided into LPS, LCAP and LCAP-sham groups. All animals were injected with LPS to induce endotoxemia. The serum levels of leucocytes, neutrophil elastase, arterial blood gas, nuclear factor-kappa B (NF-κB) subunit p65 in lung tissues were measured. The histopathology and parenchyma apoptosis of lung tissues were examined. We found that 7, 3, and 7 animals in the LPS, LCAP, and sham-LCAP groups, respectively, developed ALI 36 h after LPS infusion. The levels of NF-κB p65 in lung tissue, neutrophils and elastase in blood, decreased significantly following LCAP. LCAP also alleviated apoptosis, and NF-κB p65 in lung tissues. Collectively, our results show that partial removal of leucocytes from peripheral blood decreases elastase level in serum. This, in turn, attenuates lung injuries and may potentially decrease the incidence of ALI.

Published
2012

31. The design of analysis system of refractive index profile of optical fiber

Author

Zhihai Liu and Gao He

Subjects
Engineering, Mode volume, Optical fiber, Multi-mode optical fiber, business.industry, Single-mode optical fiber, Physics::Optics, Refractive index profile, Capacitive displacement sensor, Graded-index fiber, law.invention, Optics, law, Fiber optic sensor, business
Abstract

This paper developed an intelligent optical fiber refractive index profile measurement system. This system is based on the principle of the refracted near-field measurement. The whole system is the use of a unique high-resolution non-contact capacitive displacement sensor to monitor the scanning position of the fiber measured. At the same time we used a shading screen which was embedded into the sample pool. Using this method, we can totally save space. Finally, we used a high curvature condenser to collection of reflected light which we used a photo detector to collect. The collected signal was brought into the computer to calculate the optical fiber refractive index. The whole system is totally enclosed operating instrument with an easy-to-use software interface for performing measurements of both multi mode and single mode optical fiber, which can easy pick up the signal automatically and processing in computer. Measurement accuracy can reach 10 -4 . It is fit for measuring the refractive index of single-mode fibers and multi-mode fibers.

Published
2011

32. The interference and integration of a fiber electro-optic intensity modulator

Author

Zhihai Liu, Wang Lei, and Gao He

Subjects
Materials science, business.industry, Physics::Optics, Electro-optic modulator, Polarization-maintaining optical fiber, Graded-index fiber, Optical modulator, Optics, Fiber optic sensor, Optoelectronics, Dispersion-shifted fiber, Plastic optical fiber, business, Photonic-crystal fiber
Abstract

The newly interfere and integrated fiber electro-optic intensity modulator was researched, it was made into Michelson interferometer by thermal poled hollow two-core fiber, and researched the modulation effect of the electro-optic intensity modulator. The result indicate that the poled fiber modulator have low half-wave voltage, and achieved a good effect on intensity modulate, it also realized electro-optic fiber modulator and Michelson interferometer integrated in one optical fiber. The electro-optic intensity modulator have good stability, simple structure and so on.

Published
2011

33. Research on the Measurement of Customer Value Based on Competition-oriented

Author

Gao He

Subjects
Customer delight, Customer retention, Customer advocacy, Customer equity, Customer profitability, Customer lifetime value, Business, Marketing, Customer intelligence, Customer to customer
Abstract

In this paper, the theory of customer value throughout the entire process of research, centered on how to measure customer value and develop competitive strategy with the theory of customer value. Firstly, introduced the idea of "competition" to the theory of customer value measurement, pointed out that the measurement of customer value needs to select and integrate the existing methods, Based on empirical study, obtained two factors of perceived value attributes when consumers used the cell phones, found that three foreign brands in terms of the difference of customer perceived value was more obvious, the competition between the two domestic brands was most intense, and the customer perceived value of foreign brands was higher than domestic brands.

Published
2011

34. Establishment of expert system for Hanfu Apple Industrial Science and Technology Service System

Author

Yang Tao, Gao He, and Song Ping

Subjects
Engineering management, Service system, Service (systems architecture), Engineering, Knowledge base, business.industry, Production (economics), Inference engine, business, computer.software_genre, computer, Expert system, Simulation
Abstract

Aiming at the lack in dynamic projection function and mechanical explaination, an expert system is proposed to be established for Hanfu Apple Industrial Science and Technology Service System with the help of Hanfu Apple selected and cultivated by Shenyang Algriculture University. Detailed analyses have been performed on the demand, background and significance of research for the system. A physical expert system has been established for Hanfu Apple Industrial Science and Technology Service System, which provides wider and more convinent service for the users by taking advantage of the distribution features of network with multiple users.

Published
2011

35. How to face the economic situation in the Russian Far East in the post-crisis era for China

Author

Li Nan and Gao He

Subjects
Government, Economic indicator, Economy, Post crisis, Economic policy, Financial crisis, Face (sociological concept), Business, Investment (macroeconomics), Far East, China
Abstract

Influenced by the global financial crisis since later 2008, the economy of Russia has declined across the board. Russian GDP has fallen by about 9% in 2009. In this paper, the economy in Russian Far East grew slowly, however, the overall situation was better than the whole country's situation. With the post crisis era coming, the government and enterprises must have a clear view of local coming socio-economic situations, and prepare fully to meet the risks of trade and investment.

Published
2011

36. Study on the measurement of customer value based on means-end chain theory

Author

Gao He and Pan Chi

Subjects
Customer retention, Voice of the customer, Customer advocacy, Knowledge management, Computer science, Customer equity, business.industry, Customer lifetime value, Marketing, Business value, Customer to customer, business, Customer intelligence
Abstract

Woodruff proposed the definition of customer value based on the theory of Means-end chain reveals the nature of customer value very well, its detailed and profound discussion about learning and using the theory of customer value has far-reaching and guiding significance on the practice of business. After reviewing the literature on customer value, Means-end chain and laddering method, this research considers that based on the theory of Means-end chain we can measure the customer value better and understand the customer's expected and perceived value in different hierarchies better. Customers who purchased notebook computers were taken as the samples in this research, first proceeding qualitative research by laddering method, get multiple variables in different hierarchies, then measuring the importance of these variables by the quantitative research, obtaining value dimensions in different hierachies which customers think these are important, and in accordance with qulitative analysis to identify the linkage between the value dimensions, and draw the customer value hierarchy model based on Means-end chain. This research concluded that if an enterprise has a deep understanding of customers' value dimensions and the relationship between them, it will form competitive advantage from the ability of attracting customers, and create more value for customers.

Published
2010

37. Study of the Relationship between Service Quality, Customer Satisfaction and Behavior Intention

Author

Gao He and Liu Jun

Subjects
Customer delight, Service (business), Service quality, Customer retention, Customer advocacy, Service level objective, Advertising, Customer satisfaction, Business, Service guarantee, Marketing
Abstract

Quality of service is the core of service industry development, and is the most focused issues in service marketing research. Through reviewing the literature of service quality, this research studies the relationship of service quality, customer satisfaction and behavior intention. In this study, the railway passenger services as the empirical study object, the results show that rail passenger service quality is proven to have positive effect on customer satisfaction, and also have positive effect on behavior intention through customer satisfaction. But rail passenger service quality has no obvious effect on behavior intention.

Published
2010

38. Study on the Undergraduate Education Satisfaction of the Higher Education Institutions

Author

Rong Xiao-hua and Gao He

Subjects
Further education, Service quality, Medical education, Higher education, business.industry, Business education, Economics education, Engineering management, Marketing management, ComputingMilieux_COMPUTERSANDEDUCATION, Customer satisfaction, Education policy, business, Psychology
Abstract

The level of undergraduate education satisfaction directly reflects the service quality of higher education, and has great practical significance and value in guiding higher education institutions’ service activities. After introducing the meaning of undergraduate education satisfaction, through empirical research, this study analyzes the status and problems of undergraduate education satisfaction of higher education institutions, finds that the level of the higher education satisfaction is not high, students’ diverse needs can not be meet, and education administration department lacks of service awareness. Therefore, higher education institutions should establish a marketing management philosophy which is customer-centered, and takes students as the foremost, use marketing thinking and strive to meet the needs of students, improving the undergraduate education satisfaction of the higher education institutions.

Published
2010

39. The Study of the Competition-oriented Customer Value Measurement

Author

Gao He, Zhang Ming-li, and Wang Chun-xia

Subjects
Customer retention, Customer advocacy, Customer profitability, Value proposition, Value (economics), Customer lifetime value, Customer satisfaction, Business, Marketing, Business value
Abstract

This paper first puts forward that the measurement of customer value needs the selection and confirmative application of the existing methods. Then on the basis of positive study, the paper concludes that the consumers have two factors towards the automobile products value property and finds out that it is obvious that the consumers have higher perceived value towards the foreign brands than the national ones; meanwhile on the basis of evaluation of the competitive brands measurement property, the paper discusses the brand differences in 12 property-performances. In the market environment of more severe competition, creating prominent value for the customers has become the new source for the modern enterprises to gain the kernel competitive force and advantages. How to measure and apply customer value is the prerequisite and basis for the enterprises to implement customer value management. Therefore, it is no doubt the concern of both enterprises and intellectual circles.

Published
2006

40. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Author

Patricia A. Peyser, Jessica D. Faul, Sing Hui Lim, Xu Chen, Brian E. Cade, Patrik K. E. Magnusson, John C. Chambers, Tamar Sofer, Marzyeh Amini, Benjamin Lehne, W. James Gauderman, Wei Zhao, Andres Metspalu, R. Graham Barr, Albertine J. Oldehinkel, Xueling Sim, Norihiro Kato, Daniel I. Chasman, Jasmin Divers, Fernando Pires Hartwig, Jing Hua Zhao, Yu Caizheng, Roby Joehanes, Nora Franceschini, Nita G. Forouhi, Charumathi Sabanayagam, Paul M. Ridker, Yun J. Sung, Mary F. Feitosa, Barbara V. Howard, Vilmundur Gudnason, Jost B. Jonas, Hua Tang, Yukihide Momozawa, Michael R. Brown, Tibor V. Varga, Franco Giulianini, Francis S. Collins, Alexander P. Reiner, Ulrich Broeckel, Tuomo Rankinen, Preeti Gupta, Tin Louie, Eric Boerwinkle, Saskia P. Hagenaars, Mark J. Caulfield, Albert Hofman, Aravinda Chakravarti, Paul W. Franks, Nicole Schupf, E. Shyong Tai, Carl D. Langefeld, Carsten Oliver Schmidt, Lawrence F. Bielak, Treva Rice, Anne B. Newman, Ioanna Ntalla, Kae-Woei Liang, Nilesh J. Samani, Alena Stančáková, Thomas H. Mosley, Dan E. Arking, Kenneth Rice, Bruce M. Psaty, Jirong Long, Yechiel Friedlander, Jianjun Liu, Donna K. Arnett, Ya X. Wang, Xiuqing Guo, Anne E. Justice, Pamela J. Schreiner, Renée de Mutsert, Lisa de las Fuentes, Marcus Dörr, Amy R. Bentley, Susan Redline, Cornelia M. van Duijn, Melissa A. Richard, Sarah E. Harris, Pirjo Komulainen, Nicholette D. Palmer, Alexandre C. Pereira, Michele K. Evans, Jie Yao, Adesola Ogunniyi, Wen Bin Wei, Anuradhani Kasturiratne, Yoichiro Kamatani, Charles Kooperberg, Helen R. Warren, Shiow Lin, Ozren Polasek, Makoto Hirata, Anubha Mahajan, Yingchang Lu, Jonathan Marten, Claudia P. Cabrera, Chuan Gao, Oscar H. Franco, Yongmei Liu, Mathilde Boissel, Olli T. Raitakari, Xiao-Ou Shu, Yii-Der Ida Chen, Y Liu, Claudia Langenberg, C. Charles Gu, Cathy C. Laurie, Tamuno Alfred, L. Adrienne Cupples, Yajuan Wang, Colin A. McKenzie, Mika Kähönen, Yize Li, Xiaofeng Zhu, Nana Matoba, James Scott, Marguerite R. Irvin, Markku Laakso, Frida Renström, Woon-Puay Koh, Dabeeru C. Rao, Yucheng Jia, Paul Elliott, Tangchun Wu, Caroline Hayward, Tamara B. Harris, Alison D. Murray, Karin Leander, Reedik Mägi, Keng-Hung Lin, Harold Snieder, Laura J. Bierut, Christine Williams, Solomon K. Musani, Michael A. Province, Charles B. Eaton, Sharon L.R. Kardia, Mario Sims, Steven C. Hunt, Stephen B. Kritchevsky, Weihua Zhang, David R. Weir, Andrea R. V. R. Horimoto, Saima Afaq, Hugues Aschard, Ilaria Gandin, Michiaki Kubo, Jaspal S. Kooner, Peter S. Braund, Jeffrey R. O'Connell, Kent D. Taylor, Annette Peters, Wei Zheng, Rainer Rettig, Nicola D. Kerrison, Donald W. Bowden, Ruth J. F. Loos, Tanika N. Kelly, Dennis O. Mook-Kanamori, Terrence Forrester, Igor Rudan, Brigitte Kühnel, Christopher P. Nelson, Ching-Yu Cheng, Alanna C. Morrison, Tuomas O. Kilpeläinen, Jian-Min Yuan, Bruna Gigante, Lisa R. Yanek, Ching-Ti Liu, Ananda R. Wickremasinghe, Michael Boehnke, Tin Aung, Jin-Fang Chai, Kaare Christensen, Wen-Jane Lee, Stéphanie Debette, Jennifer A. Brody, Wayne Huey-Herng Sheu, John M. C. Connell, Ganesh Chauhan, Jian'an Luan, Melanie Waldenberger, Erin B. Ware, Paolo Gasparini, Chew-Kiat Heng, Lili Milani, Alisa K. Manning, José Eduardo Krieger, Kiang Liu, Mickaël Canouil, Robert A. Scott, Yik Ying Teo, Gregory P. Wilson, Stella Aslibekyan, Andrew P. Morris, Thomas Meitinger, Jennifer A. Smith, Yi-Jen Hung, Myriam Fornage, Dina Vojinovic, William R. Scott, Virginia Fisher, Peter S. Sever, André G. Uitterlinden, Najaf Amin, Lenore J. Launer, Hugh Watkins, Johanna Kuusisto, Rajkumar Dorajoo, Georg Ehret, Heming Wang, Sandosh Padmanabhan, Jingmin Liu, Colleen M. Sitlani, Anuj Goel, Bamidele O. Tayo, Daniel Levy, Barry I. Freedman, Marie Loh, Yanhua Zhou, Charles N. Rotimi, Qing Duan, Aldi T. Kraja, He Meian, Archie Campbell, Kari E. North, Tien Yin Wong, Salman M. Tajuddin, Traci M. Bartz, Mike A. Nalls, Misa Graff, Dongfeng Gu, Sudha Seshadri, Tõnu Esko, Antonietta Robino, Anne U. Jackson, H. Janaka de Silva, Peter J. van der Most, Fang-Chi Hsu, Chiea Chuen Khor, Changwei Li, Sami Heikkinen, Maris Alver, Karen Schwander, Wanqing Wen, Rainer Rauramaa, Lynne E. Wagenknecht, Ubaydah Nasri, Peter J. Munson, He Gao, Evangelos Evangelou, Philippe Froguel, Ervin R. Fox, Christian Gieger, Kurt Lohman, James S. Pankow, Nicholas J. Wareham, Lynda M. Rose, Massimiliano Cocca, Rob M. van Dam, John M. Starr, Martin Farrall, Stefan Weiss, Konstantin Strauch, Albert V. Smith, Jill M. Norris, Raymond Noordam, Cora E. Lewis, Claude Bouchard, Ulf de Faire, Walter Palmas, Diane M. Becker, Kevin Sandow, Tomohiro Katsuya, Jiang He, Nancy L. Pedersen, Bernardo L. Horta, Joel D. Kaufman, Terho Lehtimäki, Heikki A. Koistinen, Thomas W. Winkler, Ian J. Deary, Richard S. Cooper, Fumihiko Takeuchi, Jerome I. Rotter, Lihua Wang, Yih Chung Tham, Babatunde L. Salako, Mary K. Wojczynski, Pim van der Harst, Jennifer G. Robinson, Erwin P. Bottinger, Alan B. Zonderman, Patricia B. Munroe, Ehret, Georg Benedikt, Harvard School of Public Health, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The various Gene-Lifestyle Interaction projects, including this one, are largely supported by a grant from the U.S. National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health, R01HL118305. A Career Development Award (K25HL121091), also from the NHLBI, enabled Y.J.S. to lead this project. Full set of study-specific funding sources and acknowledgments appear in the Supplemental Note., Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpeläinen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugue, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Mari, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pire, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kähönen, Mika, Kasturiratne, Anuradhani, Kühnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, ’an Luan, Jian, Mckenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H. H., Stančáková, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickaël, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renée, de Silva, H. Janaka, Debette, Stephanie, Dörr, Marcu, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelo, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charle, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charle, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Mägi, Reedik, Mahajan, Anubha, Meitinger, Thoma, Metspalu, Andre, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, André G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tõnu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimäki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, Jame, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Kritchevsky, Stephen B., Levy, Daniel, O'Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. Jame, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., Chasman, Daniel I., Marten, Jonathan [0000-0001-6916-2014], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Epidemiology, Internal Medicine, Gastroenterology & Hepatology, Clinicum, Department of Medicine, Endokrinologian yksikkö, HUS Internal Medicine and Rehabilitation, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, multi-ancestry, Smoking/genetics, Genome-wide association study, Continental Population Groups/genetics, INTIMA-MEDIA THICKNESS, Cohort Studies, Diastole, Polymorphism (computer science), GWAS, TRANSTORNOS RELACIONADOS AO USO DE ÁLCOOL, GENE-ENVIRONMENT INTERACTION, Genetics (clinical), ddc:616, INSULIN-RESISTANCE, Multi-ancestry, Smoking, 1184 Genetics, developmental biology, physiology, blood pressure, GxE interaction, Diastole/genetics, 3. Good health, FALSE DISCOVERY RATE, Blood pressure, Medical genetics, CORONARY-ARTERY-DISEASE, Female, Single Nucleotide/genetics, Systole/genetics, BODY-MASS INDEX, ASSOCIATION ANALYSIS, COMMON VARIANTS, METAANALYSIS, DISEASE, OBESITY, JOINT, medicine.medical_specialty, lifestyle, SUSCEPTIBILITY LOCI, Blood Pressure/genetics, Systole, Quantitative Trait Loci, Single-nucleotide polymorphism, Accounting, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, GxE interactions, Article, smoking, 03 medical and health sciences, Genetic, medicine, Genetics, Journal Article, Humans, Polymorphism, Genetic association, ALCOHOL DEPENDENCE, business.industry, Racial Groups, Reproducibility of Results, Epistasis, Genetic, ta3121, Lifestyle, Genetic architecture, NICOTINE DEPENDENCE, 030104 developmental biology, Genetic Loci, Epistasis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, business, Quantitative Trait Loci/genetics, Genome-Wide Association Study
Abstract

The authors declare no competing financial interests except for the following. B.M.P. serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson; O.H.F. received grants from Metagenics (on women’s health and epigenetics) and from Nestle (on child health); L.J.B. is listed as an inventor on Issued U.S. Patent 8,080,371,“Markers for Addiction” covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction; P.S. has received research awards from Pfizer Inc., is a consultant for Mundipharma Co. (Cambridge, UK), is a patent holder with Biocompatibles UK Ltd. (Franham, Surrey, UK) (Title: Treatment of eye diseases using encapsulated cells encoding and secreting neuroprotective factor and/or anti-angiogenic factor; Patent number: 20120263794), and has a patent application with University of Heidelberg (Heidelberg, Germany) (Title: Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia; Europäische Patentanmeldung 15 000 771.4); P.W.F. has been a paid consultant for Eli Lilly and Sanofi Aventis and has received research support from several pharmaceutical companies as part of a European Union Innovative Medicines Initiative (IMI) project; M.A.N.’s participation is supported by a consulting contract between Data Tecnica Internation and the National Institute on Aging (NIH, Bethesda, MD, USA), and he also consults for Illumina, Inc., the Michael J. Fox Foundation, and University of California Healthcare among others; and M.J.C. is Chief Scientist for Genomics England, a UK government company.; International audience; Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined approximately 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

Published
2018

41. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author

Rico Rueedi, Yuri Milaneschi, Brenda W.J.H. Penninx, Neil Poulter, Karen Schwander, Marco Brumat, Kenneth Rice, Yize Li, Veronique Vitart, Ioanna Ntalla, Michele K. Evans, Jeffrey R. O'Connell, Nilesh J. Samani, Colleen M. Sitlani, W. James Gauderman, Xuan Deng, Paul M. Ridker, Yun J. Sung, Yukihide Momozawa, Archie Campbell, Tin Louie, Nona Sotoodehnia, Yii-Der Ida Chen, Cornelia M. van Duijn, Tanika N. Kelly, Peter S. Sever, André G. Uitterlinden, Brigitte Kühnel, John M. Starr, Lawrence F. Bielak, Christopher P. Nelson, Wanqing Wen, Stephan B. Felix, Stefan Weiss, Daniel Levy, Nicholette D. Palmer, Alisa K. Manning, Salman M. Tajuddin, Jill M. Norris, Marie Loh, M. Abdullah Said, Alena Stančáková, Anuradhani Kasturiratne, John M. C. Connell, Jian'an Luan, Tuomas O. Kilpeläinen, Amy R. Bentley, Stephen Sidney, Alan B. Zonderman, Karin Leander, David J. Porteous, Jianjun Liu, Tin Aung, Charles B. Eaton, Sharon L.R. Kardia, Rajkumar Dorajoo, Stephen Turner, Michael Boehnke, Diane M. Becker, Cora E. Lewis, Ozren Polasek, Mickaël Canouil, Kurt Lohman, Georg Ehret, Sarah E. Harris, Robert A. Scott, Claude Bouchard, Lynne E. Wagenknecht, Mohsen Ghanbari, Stephen B. Kritchevsky, Jin-Fang Chai, Gregory L. Burke, Jiang He, Federica Laguzzi, Michael R. Brown, Walter Palmas, Lili Milani, Thomas T. Perls, Tibor V. Varga, José Eduardo Krieger, Erin B. Ware, Tamara B. Harris, Tomohiro Katsuya, Nicole Schupf, Mika Kähönen, Nana Matoba, Hugues Aschard, Ilaria Gandin, Jennifer A. Smith, Traci M. Bartz, James Scott, Tuomo Rankinen, Yuan Shi, Meian He, Timo A. Lakka, Helen R. Warren, Mike A. Nalls, Kent D. Taylor, Woon-Puay Koh, Ya Xing Wang, Muhammad Riaz, Sandosh Padmanabhan, Mary F. Feitosa, Jost B. Jonas, Paul Elliott, Christian Gieger, Terho Lehtimäki, Kaare Christensen, Maris Alver, Pirjo Komulainen, Pamela J. Schreiner, M. Arfan Ikram, David R. Weir, Charles Kooperberg, Oscar H. Franco, Yongmei Liu, Lisa de las Fuentes, Nancy L. Pedersen, Thomas W. Winkler, Bruna Gigante, Göran Hallmans, Ingrid B. Borecki, Shiow Lin, Ian J. Deary, Wei Zheng, Yajuan Wang, Bernardo L. Horta, Heather M. Stringham, Bruce M. Psaty, Paul W. Franks, Weihua Zhang, Nora Franceschini, Adolfo Correa, Nita G. Forouhi, Xiuqing Guo, Fumihiko Takeuchi, L. Adrienne Cupples, William R. Scott, Zoltán Kutalik, He Gao, Nicholas J. Wareham, E. Shyong Tai, Aravinda Chakravarti, C. Charles Gu, Paolo Gasparini, Albertine J. Oldehinkel, Xueling Sim, Norihiro Kato, Evangelos Evangelou, Philippe Froguel, Colin A. McKenzie, Qing Duan, Aldi T. Kraja, Carsten Oliver Schmidt, Bamidele O. Tayo, Xiaofeng Zhu, Thomas Meitinger, Mary K. Wojczynski, Markku Laakso, Mark J. Caulfield, Carl D. Langefeld, Jingzhong Ding, Yechiel Friedlander, Tien Yin Wong, Virginia Fisher, Raymond Noordam, Caizheng Yu, Pim van der Harst, Yik Ying Teo, Ervin R. Fox, Sabanayagam Charumathi, Jonathan Marten, Nicholas Y.Q. Tan, Jerome I. Rotter, Harold Snieder, Karen L. Mohlke, Christine Williams, Olli T. Raitakari, Renée de Mutsert, Lihua Wang, Kathryn Roll, Jingmin Liu, Dongfeng Gu, Wei Zhao, Lynda M. Rose, Michael A. Province, Fernando Pires Hartwig, Rob M. van Dam, Barry I. Freedman, Andres Metspalu, Donald W. Bowden, Andrea R. V. R. Horimoto, Martin Farrall, Frits R. Rosendaal, Rainer Rauramaa, Konstantin Strauch, Albert V. Smith, Yanick Hagemeijer, Michiaki Kubo, Ilja M. Nolte, Tõnu Esko, Yih Chung Tham, Cathy C. Laurie, Antonietta Robino, Anne U. Jackson, Chuan Gao, Dabeeru C. Rao, Xiao-Ou Shu, H. Janaka de Silva, Morris J. Brown, Alanna C. Morrison, Peter J. van der Most, Jian-Min Yuan, Melanie Waldenberger, Leslie J. Raffel, Ulrich John, Fang-Chi Hsu, Reedik Mägi, Solomon K. Musani, Chiea Chuen Khor, Mario Sims, Ruben N. Eppinga, Melissa A. Richard, Yoichiro Kamatani, Changwei Li, Qiuyin Cai, Daniel I. Chasman, Mathilde Boissel, Claudia Langenberg, Sami Heikkinen, Jasmin Divers, Saima Afaq, Wen Bin Wei, Jaspal S. Kooner, Terrence Forrester, Hua Tang, Charles N. Rotimi, Anuj Goel, Annette Peters, Tangchun Wu, Dennis O. Mook-Kanamori, Caroline Hayward, Ching-Yu Cheng, Lisa R. Yanek, Ananda R. Wickremasinghe, Chew-Kiat Heng, Myriam Fornage, Dina Vojinovic, Najaf Amin, Lenore J. Launer, Hugh Watkins, Johanna Kuusisto, Jing Hua Zhao, Barbara V. Howard, Vilmundur Gudnason, Ulrich Broeckel, Eric Boerwinkle, Saskia P. Hagenaars, Dan E. Arking, Peter Vollenweider, Alexandre C. Pereira, Jie Yao, Makoto Hirata, Patricia B. Munroe, Patricia A. Peyser, Jessica D. Faul, Xu Chen, Patrik K. E. Magnusson, John C. Chambers, Tamar Sofer, Marzyeh Amini, Benjamin Lehne, Epidemiology, Erasmus MC other, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), School of Health Sciences (UI), Heilbrigðisvísindasvið (HÍ), Háskóli Íslands (HÍ), University of Iceland (UI), Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), University of Regensburg, Queen Mary University of London (QMUL), Harbor UCLA Medical Center [Torrance, Ca.], Department of Epidemiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Northwestern Polytechnical University [Xi'an] (NPU), Centre for Molecular Epidemiology, National University of Singapore (NUS), Harvard School of Public Health, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), National Institutes of Health [Bethesda] (NIH), The following authors declare commercial private and/or governmental affiliations: Bruce M. Psaty (BMP) serves on the DSMB of a clinical trial funded by Zoll Lifecor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Barbara V. Howard (BVH) has a contract from National Heart, Lung, and Blood Institute (NHLBI). Brenda W.J.H. Penninx (BWJHP) has received research funding (non-related to the work reported here) from Jansen Research and Boehringer Ingelheim. Mike A. Nalls (MAN) is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. MAN also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. MAN also has commercial affiliation with Data Tecnica International, Glen Echo, MD, USA. Mark J. Caulfield (MJC) has commercial affiliation and is Chief Scientist for Genomics England, a UK government company. Oscar H Franco (OHF) is supported by grants from Metagenics (on women's health and epigenetics) and from Nestlé (on child health). Peter S. Sever (PSS) is financial supported from several pharmaceutical companies which manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. Paul W. Franks (PWF) has been a paid consultant in the design of a personalized nutrition trial (PREDICT) as part of a private-public partnership at Kings College London, UK, and has received research support from several pharmaceutical companies as part of European Union Innovative Medicines Initiative (IMI) projects. Fimlab LTD provided support in the form of salaries for author Terho Lehtimäki (TL) but did not have any additional role in the study design to publish, or preparation of the manuscript. Gen‐info Ltd provided support in the form of salaries for author Ozren Polašek (OP) but did not have any additional role in the study design to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. There are no patents, products in development, or marked products to declare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., AGES (Age Gene/Environment Susceptibility Reykjavik Study) is approved by the Icelandic National Bioethics Committee, VSN: 00–063. The researchers are indebted to the participants for their willingness to participate in the study. ARIC (Atherosclerosis Risk in Communities): The authors thank the staff and participants of the ARIC study for their important contributions. CARDIA (Coronary Artery Risk Development in Young Adults): This manuscript has been reviewed and approved by CARDIA for scientific content. CHS (Cardiovascular Health Study): A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. IGMM (Institute of Genetics and Molecular Medicine): CROATIA-Korcula: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools and the Croatian Institute for Public Health. We would like to acknowledge the invaluable contributions of the recruitment team in Korcula, the administrative teams in Croatia and Edinburgh and the participants. The SNP genotyping for the CROATIA-Korcula cohort was performed in Helmholtz Zentrum München, Neuherberg, Germany. CROATIA-Vis: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools, the Institute for Anthropological Research in Zagreb and Croatian Institute for Public Health. The SNP genotyping for the CROATIA-Vis cohort was performed in the core genotyping laboratory of the Wellcome Trust Clinical Research Facility at the Western General Hospital, Edinburgh, Scotland. GS:SFHS: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland. ERF (Erasmus Rucphen Family study): We are grateful to all study participants and their relatives, general practitioners and neurologists for their contributions and to P. Veraart for her help in genealogy, J. Vergeer for the supervision of the laboratory work, P. Snijders for his help in data collection and E.M. van Leeuwen for genetic imputation. GENOA (Genetic Epidemiology Network of Arteriopathy): Genotyping was performed at the Mayo Clinic (Stephen T. Turner, MD, Mariza de Andrade PhD, Julie Cunningham, PhD). We thank Eric Boerwinkle, PhD and Megan L. Grove from the Human Genetics Center and Institute of Molecular Medicine and Division of Epidemiology, University of Texas Health Science Center, Houston, Texas, USA for their help with genotyping. We would also like to thank the families that participated in the GENOA study. HANDLS (Healthy Aging in Neighborhoods of Diversity across the Life Span): Data analyses for the HANDLS study utilized the high-performance computational resources of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD. http://hpc.nih.gov HUFS (Howard University Family Study): We thank the participants of the study. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. HyperGEN (Hypertension Genetic Epidemiology Network): The study involves: University of Utah: (Network Coordinating Center, Field Center, and Molecular Genetics Lab), Univ. of Alabama at Birmingham: (Field Center and Echo Coordinating and Analysis Center), Medical College of Wisconsin: (Echo Genotyping Lab), Boston University: (Field Center), University of Minnesota: (Field Center and Biochemistry Lab), University of North Carolina: (Field Center), Washington University: (Data Coordinating Center), Weil Cornell Medical College: (Echo Reading Center), National Heart, Lung, & Blood Institute. For a complete list of HyperGEN Investigators: http://www.biostat.wustl.edu/hypergen/Acknowledge.html JHS (Jackson Heart Study): The authors wish to thank the staffs and participants of the JHS. MESA (Multi-Ethnic Study of Atherosclerosis): MESA and the MESA SHARe project are conducted in collaboration with MESA investigators. Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. NEO (The Netherlands Epidemiology of Obesity study): The authors of the NEO study thank all individuals who participated in the Netherlands Epidemiology in Obesity study, all participating general practitioners for inviting eligible participants and all research nurses for collection of the data. We thank the NEO study group, Petra Noordijk, Pat van Beelen and Ingeborg de Jonge for the coordination, lab and data management of the NEO study. RS (Rotterdam Study) was funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera, Marjolein Peters and Carolina Medina-Gomez for their help in creating the GWAS database, and Karol Estrada, Yurii Aulchenko and Carolina Medina-Gomez for the creation and analysis of imputed data. WHI (Women’s Health Initiative): The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf Replication: AA-DHS (African American Diabetes Heart Study): The investigators acknowledge the cooperation of our Diabetes Heart Study (DHS) and AA-DHS participants. ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial): We thank all ASCOT trial participants, physicians, nurses, and practices in the participating countries for their important contribution to the study. In particular, we thank Clare Muckian and David Toomey for their help in DNA extraction, storage, and handling. We would also like to acknowledge the Barts and The London Genome Centre staff for genotyping the Exome chip array. P.B.M, M.J.C and H.R.W wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Centre at Barts and Queen Mary University of London, UK. BBJ (Biobank Japan Project): We thank all the participants, medical coordinators of the cooperating hospitals for collecting samples and clinical information in the project. BRIGHT (British Genetics of Hypertension): The BRIGHT study is extremely grateful to all the patients who participated in the study and the BRIGHT nursing team. P.B.M, M.J.C and H.R.W wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Centre at Barts and Queen Mary University of London, UK. CoLaus (Cohorte Lausannoise Study): The authors would like to thank all the people who participated in the recruitment of the participants, data collection and validation, particularly Nicole Bonvin, Yolande Barreau, Mathieu Firmann, François Bastardot, Julien Vaucher, Panagiotis Antiochos and Cédric Gubelmann. DESIR (Data from an Epidemiological Study on the Insulin Resistance): The DESIR Study Group is composed of Inserm-U1018 (Paris: B. Balkau, P. Ducimetière, E. Eschwège), Inserm-U367 (Paris: F. Alhenc-Gelas), CHU d’Angers (A. Girault), Bichat Hospital (Paris: F. Fumeron, M. Marre, R. Roussel), CHU de Rennes (F. Bonnet), CNRS UMR-8199 (Lille: A. Bonnefond, P. Froguel), Medical Examination Services (Alençon, Angers, Blois, Caen, Chartres, Chateauroux, Cholet, LeMans, Orléans and Tours), Research Institute for General Medicine (J. Cogneau), the general practitioners of the region and the Cross- Regional Institute for Health (C. Born, E. Caces, M. Cailleau, N. Copin, J.G. Moreau, F. Rakotozafy, J. Tichet, S. Vol). DHS (Diabetes Heart Study): The authors thank the investigators, staff, and participants of the DHS for their valuable contributions. EGCUT Estonian Genome Center—University of Tartu (Estonian Biobank): Data analyzes were carried out in part in the High Performance Computing Center of University of Tartu. EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk: We thank all EPIC participants and staff for their contribution to the study. FENLAND (The Fenland Study): We are grateful to all the volunteers for their time and help, and to the General Practitioners and practice staff for assistance with recruitment. We thank the Fenland Study Investigators, Fenland Study Co-ordination team and the Epidemiology Field, Data and Laboratory teams. We further acknowledge support from the Medical research council (MC_UU_12015/1). GeneSTAR (Genetic Studies of Atherosclerosis Risk): We are very grateful to all of our participants for their long-term involvement. GLACIER (Gene x Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk): We thank the participants, health professionals and data managers involved in the Västerbottens Intervention Project. We are also grateful to the staff of the Northern Sweden Biobank for preparing materials and to K Enqvist and T Johansson (Västerbottens County Council, Umeå, Sweden) for DNA preparation. HCHS/SOL (Hispanic Community Health Study/Study of Latinos): We thank the participants and staff of the HCHS/SOL study for their contributions to this study. HRS (Health & Retirement Study): Our genotyping was conducted by the NIH Center for Inherited Disease Research (CIDR) at Johns Hopkins University. Genotyping quality control and final preparation of the data were performed by the Genetics Coordinating Center at the University of Washington. HyperGEN-AXIOM (Hypertension Genetic Epidemiology Network—Axiom Chip GWAS): We thank the study investigators, staff and participants for their value contributions. INGI (Italian Network Genetic Isolate): We thank all the inhabitants who participated to the projects. InterAct (The EPIC-InterAct Case-Cohort Study): We thank all EPIC participants and staff for their contribution to the study. IRAS (Insulin Resistance Atherosclerosis Study): The authors thank study investigators, staff, and participants for their valuable contributions. KORA (Cooperative Health Research in the Augsburg Region): We thank all KORA participants and staff for their contribution to the study. LBC1921 (Lothian Birth Cohort 1921): We thank the LBC1921 cohort participants and team members who contributed to these studies. Funding from the Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. LBC1936 (Lothian Birth Cohort 1936): We thank the LBC1936 cohort participants and team members who contributed to these studies. Funding from the Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. LifeLines (Lifelines Cohort Study): The authors wish to acknowledge the services of the Lifelines, the contributing research centers delivering data to Lifelines, and all the study participants. The authors wish to acknowledge the services of the Lifelines, the contributing research centers delivering data to Lifelines, and all the study participants. Also, Lifelines acknowledges the contributions from Behrooz Z Alizadeh (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), H Marike Boezen (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), Lude Franke (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands), Pim van der Harst (Department of Cardiology, University of Groningen, University Medical Center Groningen, The Netherlands), Gerjan Navis (Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands), Marianne Rots (Department of Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands), Harold Snieder (Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands), Morris Swertz (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands), Bruce HR Wolffenbuttel (Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands), Cisca Wijmenga (Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands). LLFS (Long Life Family Study): The LLFS would like to thank the participants and research staff who make the study possible. LOLIPOP (London Life Sciences Prospective Population Study): We acknowledge support of the MRC-PHE Centre for Environment and Health, and the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards. The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the Imperial College Healthcare NHS Trust, the NHS, the NIHR or the Department of Health. We thank the participants and research staff who made the study possible. PROCARDIS (Precocious Coronary Artery Disease): The PROCARDIS researchers thank the patients for their selfless participation in this project. RHS (Ragama Health Study): The RHS was supported by the Grant of National Center for Global Health and Medicine (NCGM), Japan. SWHS/SMHS (Shanghai Women's Health Study/ Shanghai Men's Health Study): We thank all the individuals who took part in these studies and all the researchers who have enabled this work to be carried out. TRAILS (TRacking Adolescents’ Individual Lives Survey): TRAILS is a collaborative project involving various departments of the University Medical Center and University of Groningen, the Erasmus University Medical Center Rotterdam, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands. We are grateful to all adolescents who participated in this research and to everyone who worked on this project and made it possible. UKB (United Kingdom Biobank, www.ukbiobank.ac.uk): This research has been conducted using the UK Biobank Resource. The UK Biobank data were analyzed from the data set corresponding to UK Biobank access application no. 236, application title 'Genome-wide association study of blood pressure', with Paul Elliott as the PI/applicant. This work was supported by the UK-CMC and the BP working group., InterAct Consortium, Marten, Jonathan [0000-0001-6916-2014], Luan, Jian'an [0000-0003-3137-6337], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Lee Kong Chian School of Medicine (LKCMedicine), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Feitosa, Mary F., Kraja, Aldi T., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Bentley, Amy R., Brown, Michael R., Schwander, Karen, Richard, Melissa A., Noordam, Raymond, Aschard, Hugue, Bartz, Traci M., Bielak, Lawrence F., Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P., Horimoto, Andrea R. V. R., Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Wojczynski, Mary K., Alver, Mari, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., He, Meian, Hsu, Fang-Chi, Jackson, Anne U., Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'An, Matoba, Nana, Nolte, Ilja M., Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., Van Der Most, Peter J., Varga, Tibor V., Vitart, Veronique, Wang, Yajuan, Ware, Erin B., Warren, Helen R., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morri, Brumat, Marco, Burke, Gregory L., Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., Correa, Adolfo, De Las Fuentes, Lisa, De Mutsert, Renée, De Silva, H. Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B., Ehret, Georg, Eppinga, Ruben N., Evangelou, Evangelo, Faul, Jessica D., Felix, Stephan B., Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gigante, Bruna, Gu, C. Charle, Gu, Dongfeng, Hagenaars, Saskia P., Hallmans, Göran, Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Howard, Barbara V., Ikram, M. Arfan, John, Ulrich, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon-Puay, Krieger, José E., Kritchevsky, Stephen B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lin, Shiow, Liu, Jianjun, Liu, Jingmin, Loh, Marie, Louie, Tin, Mägi, Reedik, Mckenzie, Colin A., Meitinger, Thoma, Metspalu, Andre, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Momozawa, Yukihide, Nalls, Mike A., Nelson, Christopher P., Sotoodehnia, Nona, Norris, Jill M., O'Connell, Jeff R., Palmer, Nicholette D., Perls, Thoma, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Roll, Kathryn, Rose, Lynda M., Rosendaal, Frits R., Rotter, Jerome I., Schmidt, Carsten O., Schreiner, Pamela J., Schupf, Nicole, Scott, William R., Sever, Peter S., Shi, Yuan, Sidney, Stephen, Sims, Mario, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Stringham, Heather M., Tan, Nicholas Y. Q., Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Turner, Stephen T., Uitterlinden, André G., Vollenweider, Peter, Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Williams, Christine, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tõnu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Kutalik, Zoltán, Laakso, Markku, Laurie, Cathy C., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Polasek, Ozren, Porteous, David J., Rauramaa, Rainer, Samani, Nilesh J., Scott, Jame, Shu, Xiao-Ou, Van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Bouchard, Claude, Christensen, Kaare, Evans, Michele K., Gudnason, Vilmundur, Horta, Bernardo L., Kardia, Sharon L. R., Liu, Yongmei, Pereira, Alexandre C., Psaty, Bruce M., Ridker, Paul M., Van Dam, Rob M., Gauderman, W. Jame, Zhu, Xiaofeng, Mook-Kanamori, Dennis O., Fornage, Myriam, Rotimi, Charles N., Cupples, L. Adrienne, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Kooperberg, Charle, Palmas, Walter, Rice, Kenneth, Morrison, Alanna C., Elliott, Paul, Caulfield, Mark J., Munroe, Patricia B., Rao, Dabeeru C., Province, Michael A., Levy, Daniel, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Surgery, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, and Ehret, Georg Benedikt

Subjects
Genetics and Molecular Biology (all), Male, Erfðagreining, Áfengissýki, LOCI, Social Sciences, Blood Pressure, Genome-wide association study, Biochemistry, Vascular Medicine, TRANSCRIPTION FACTOR GATA4, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), DEPENDENCE, HEPATOCELLULAR-CARCINOMA, 80 and over, Psychology, Public and Occupational Health, Alcohol consumption, Cardiac and Cardiovascular Systems, Gene–environment interaction, ddc:616, Aged, 80 and over, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Middle Aged, Kardiologi, MESH: Polymorphism, Single Nucleotide, Áfengisneysla, MESH: Gene-Environment Interaction, COMMON VARIANTS, Genomics, MESH: Blood Pressure, Pedigree, 3. Good health, Näringslära, MESH: Young Adult, Physical Sciences, Medicine, Medical genetics, Erfðarannsóknir, Statistics (Mathematics), medicine.medical_specialty, Blood Pressure/genetics, Alcohol Drinking, MESH: Pedigree, Science, Genetic loci, ta3111, Genome Complexity, 03 medical and health sciences, Gene mapping, Genetics, Humans, Polymorphism, Statistical Methods, GENOME-WIDE ASSOCIATION, Molecular Biology Techniques, Molecular Biology, Alleles, Aged, MESH: Adolescent, MESH: Humans, Adolescent, Adult, Alcohol Drinking/epidemiology, Alcohol Drinking/genetics, Cohort Studies, Continental Population Groups/genetics, Continental Population Groups/statistics & numerical data, Female, Gene-Environment Interaction, Genetic Predisposition to Disease/epidemiology, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Hypertension/epidemiology, Hypertension/genetics, Middle Aged, Polymorphism, Single Nucleotide, Young Adult, Gene Mapping, Racial Groups, ta1182, Biology and Life Sciences, Computational Biology, MESH: Adult, Meta-analysis, 030104 developmental biology, Genetic Loci, MESH: Genome-Wide Association Study, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, Mathematics, MESH: Alcohol Drinking, Meta-Analysis, 0301 basic medicine, MESH: Continental Population Groups, MESH: Hypertension, Mathematical and Statistical Techniques, MESH: Aged, 80 and over, Polymorphism (computer science), Medicine and Health Sciences, FUNCTIONAL VARIATION, MESH: Cohort Studies, MESH: Aged, Alcohol Consumption, Multidisciplinary, Nutrition and Dietetics, MESH: Genetic Predisposition to Disease, Genetic Predisposition to Disease/epidemiology/genetics, Single Nucleotide, Blóðþrýstingur, ENVIRONMENT INTERACTION, PTP4A1-PHF3-EYS VARIANTS, Alcoholism, ANCESTRAIS, Háþrýstingur, Hypertension, Blood pressure, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Medical Genetics, Research Article, Substance-Related Disorders, Addiction, RISK, METAANALYSIS, Research and Analysis Methods, Mental Health and Psychiatry, medicine, Medicine [Science], Genetic Predisposition to Disease, Allele, Hypertension/epidemiology/genetics, Nutrition, Medicinsk genetik, Continental Population Groups/genetics/statistics & numerical data, business.industry, Alcohol Drinking/epidemiology/genetics, Genetic architecture, MESH: Male, Introns, Diet, BODY-MASS INDEX, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Publisher's version (útgefin grein)., Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10−5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10−8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension., The following authors declare commercial private and/or governmental affiliations: Bruce M. Psaty (BMP) serves on the DSMB of a clinical trial funded by Zoll Lifecor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Barbara V. Howard (BVH) has a contract from National Heart, Lung, and Blood Institute (NHLBI). Brenda W.J.H. Penninx (BWJHP) has received research funding (non-related to the work reported here) from Jansen Research and Boehringer Ingelheim. Mike A. Nalls (MAN) is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. MAN also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. MAN also has commercial affiliation with Data Tecnica International, Glen Echo, MD, USA. Mark J. Caulfield (MJC) has commercial affiliation and is Chief Scientist for Genomics England, a UK government company. Oscar H Franco (OHF) is supported by grants from Metagenics (on women's health and epigenetics) and from Nestlé (on child health). Peter S. Sever (PSS) is financial supported from several pharmaceutical companies which manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. Paul W. Franks (PWF) has been a paid consultant in the design of a personalized nutrition trial (PREDICT) as part of a private-public partnership at Kings College London, UK, and has received research support from several pharmaceutical companies as part of European Union Innovative Medicines Initiative (IMI) projects. Fimlab LTD provided support in the form of salaries for author Terho Lehtimäki (TL) but did not have any additional role in the study design to publish, or preparation of the manuscript. Gen‐info Ltd provided support in the form of salaries for author Ozren Polašek (OP) but did not have any additional role in the study design to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. There are no patents, products in development, or marked products to declare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2018

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