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1. Rare coding variants in RCN3 are associated with blood pressure

Author

He, Karen Y, Kelly, Tanika N, Wang, Heming, Liang, Jingjing, Zhu, Luke, Cade, Brian E, Assimes, Themistocles L, Becker, Lewis C, Beitelshees, Amber L, Bielak, Lawrence F, Bress, Adam P, Brody, Jennifer A, Chang, Yen-Pei Christy, Chang, Yi-Cheng, de Vries, Paul S, Duggirala, Ravindranath, Fox, Ervin R, Franceschini, Nora, Furniss, Anna L, Gao, Yan, Guo, Xiuqing, Haessler, Jeffrey, Hung, Yi-Jen, Hwang, Shih-Jen, Irvin, Marguerite Ryan, Kalyani, Rita R, Liu, Ching-Ti, Liu, Chunyu, Martin, Lisa Warsinger, Montasser, May E, Muntner, Paul M, Mwasongwe, Stanford, Naseri, Take, Palmas, Walter, Reupena, Muagututi’a Sefuiva, Rice, Kenneth M, Sheu, Wayne H-H, Shimbo, Daichi, Smith, Jennifer A, Snively, Beverly M, Yanek, Lisa R, Zhao, Wei, Blangero, John, Boerwinkle, Eric, Chen, Yii-Der Ida, Correa, Adolfo, Cupples, L Adrienne, Curran, Joanne E, Fornage, Myriam, He, Jiang, Hou, Lifang, Kaplan, Robert C, Kardia, Sharon LR, Kenny, Eimear E, Kooperberg, Charles, Lloyd-Jones, Donald, Loos, Ruth JF, Mathias, Rasika A, McGarvey, Stephen T, Mitchell, Braxton D, North, Kari E, Peyser, Patricia A, Psaty, Bruce M, Raffield, Laura M, Rao, DC, Redline, Susan, Reiner, Alex P, Rich, Stephen S, Rotter, Jerome I, Taylor, Kent D, Tracy, Russell, Vasan, Ramachandran S, Morrison, Alanna C, Levy, Daniel, Chakravarti, Aravinda, Arnett, Donna K, and Zhu, Xiaofeng

Subjects
Biological Sciences, Genetics, Cardiovascular, Human Genome, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Blood Pressure, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Precision Medicine, Whole Genome Sequencing, Rare variant analysis, Blood pressure, Whole genome sequencing, Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Information and Computing Sciences, Medical and Health Sciences, Bioinformatics, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundWhile large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries.ResultsAssociations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10- 7).ConclusionsLow frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.

Published
2022

2. Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension

Author

Kelly, Tanika N, Sun, Xiao, He, Karen Y, Brown, Michael R, Taliun, Sarah A Gagliano, Hellwege, Jacklyn N, Irvin, Marguerite R, Mi, Xuenan, Brody, Jennifer A, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, de Vries, Paul S, Gao, Yan, Moscati, Arden, Nadkarni, Girish N, Yanek, Lisa R, Elfassy, Tali, Smith, Jennifer A, Chung, Ren-Hua, Beitelshees, Amber L, Patki, Amit, Aslibekyan, Stella, Blobner, Brandon M, Peralta, Juan M, Assimes, Themistocles L, Palmas, Walter R, Liu, Chunyu, Bress, Adam P, Huang, Zhijie, Becker, Lewis C, Hwa, Chii-Min, O’Connell, Jeffrey R, Carlson, Jenna C, Warren, Helen R, Das, Sayantan, Giri, Ayush, Martin, Lisa W, Johnson, W Craig, Fox, Ervin R, Bottinger, Erwin P, Razavi, Alexander C, Vaidya, Dhananjay, Chuang, Lee-Ming, Chang, Yen-Pei C, Naseri, Take, Jain, Deepti, Kang, Hyun Min, Hung, Adriana M, Srinivasasainagendra, Vinodh, Snively, Beverly M, Gu, Dongfeng, Montasser, May E, Reupena, Muagututi A Sefuiva, Heavner, Benjamin D, LeFaive, Jonathon, Hixson, James E, Rice, Kenneth M, Wang, Fei Fei, Nielsen, Jonas B, Huang, Jianfeng, Khan, Alyna T, Zhou, Wei, Nierenberg, Jovia L, Laurie, Cathy C, Armstrong, Nicole D, Shi, Mengyao, Pan, Yang, Stilp, Adrienne M, Emery, Leslie, Wong, Quenna, Hawley, Nicola L, Minster, Ryan L, Curran, Joanne E, Munroe, Patricia B, Weeks, Daniel E, North, Kari E, Tracy, Russell P, Kenny, Eimear E, Shimbo, Daichi, Chakravarti, Aravinda, Rich, Stephen S, Reiner, Alex P, Blangero, John, Redline, Susan, Mitchell, Braxton D, Rao, Dabeeru C, Chen, Yii-Der Ida, Kardia, Sharon LR, Kaplan, Robert C, Mathias, Rasika A, He, Jiang, Psaty, Bruce M, Fornage, Myriam, Loos, Ruth JF, Correa, Adolfo, Boerwinkle, Eric, Rotter, Jerome I, Kooperberg, Charles, and Edwards, Todd L

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Good Health and Well Being, Blood Pressure, Genome-Wide Association Study, Genomics, Humans, Hypertension, Polymorphism, Single Nucleotide, Precision Medicine, allele, blood pressure, genome, hypertension, whole genome sequencing, Samoan Obesity, Lifestyle, and Genetic Adaptations Study (OLaGA) Group, ‡ NHLBI Trans-Omics for Precision Medicine TOPMed) Consortium, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundThe availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.MethodsWe conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.ResultsTwo blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P

Published
2022

3. Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data

Author

He, Karen Y, Li, Xiaoyin, Kelly, Tanika N, Liang, Jingjing, Cade, Brian E, Assimes, Themistocles L, Becker, Lewis C, Beitelshees, Amber L, Bress, Adam P, Chang, Yen-Pei Christy, Chen, Yii-Der Ida, de Vries, Paul S, Fox, Ervin R, Franceschini, Nora, Furniss, Anna, Gao, Yan, Guo, Xiuqing, Haessler, Jeffrey, Hwang, Shih-Jen, Irvin, Marguerite Ryan, Kalyani, Rita R, Liu, Ching-Ti, Liu, Chunyu, Martin, Lisa Warsinger, Montasser, May E, Muntner, Paul M, Mwasongwe, Stanford, Palmas, Walter, Reiner, Alex P, Shimbo, Daichi, Smith, Jennifer A, Snively, Beverly M, Yanek, Lisa R, Boerwinkle, Eric, Correa, Adolfo, Cupples, L Adrienne, He, Jiang, Kardia, Sharon LR, Kooperberg, Charles, Mathias, Rasika A, Mitchell, Braxton D, Psaty, Bruce M, Vasan, Ramachandran S, Rao, DC, Rich, Stephen S, Rotter, Jerome I, Wilson, James G, Chakravarti, Aravinda, Morrison, Alanna C, Levy, Daniel, Arnett, Donna K, Redline, Susan, and Zhu, Xiaofeng

Subjects
Biological Sciences, Genetics, Biotechnology, Heart Disease, Human Genome, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Alternative Splicing, Blood Pressure, Chromosomes, Human, Pair 16, Exome, Female, Follow-Up Studies, Genetic Linkage, Genetic Variation, Genome, Human, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Male, RNA Splicing Factors, Recombinases, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Blood Pressure Working Group, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p

Published
2019

4. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results

Author

Motzer, Robert J, Ravaud, Alain, Patard, Jean-Jacques, Pandha, Hardev S, George, Daniel J, Patel, Anup, Chang, Yen-Hwa, Escudier, Bernard, Donskov, Frede, Magheli, Ahmed, Carteni, Giacomo, Laguerre, Brigitte, Tomczak, Piotr, Breza, Jan, Gerletti, Paola, Lechuga, Mariajose, Lin, Xun, Casey, Michelle, Serfass, Lucile, Pantuck, Allan J, and Staehler, Michael

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Kidney Disease, Clinical Trials and Supportive Activities, Clinical Research, Cancer, Genetics, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Angiogenesis Inhibitors, Carcinoma, Renal Cell, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Humans, Indoles, Kaplan-Meier Estimate, Kidney Neoplasms, Male, Middle Aged, Nephrectomy, Proportional Hazards Models, Pyrroles, Risk Factors, Sunitinib, Time Factors, Treatment Outcome, Adjuvant, Disease-free survival, Renal cell carcinoma, Urology & Nephrology, Clinical sciences
Abstract

BackgroundAdjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03).ObjectiveTo report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS).Design, setting, and participantsData for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial.Outcome measurements and statistical analysisSubgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade.Results and limitationsOf 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively.ConclusionsA benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy.Patient summaryMost subgroups of patients at high risk of recurrent renal cell carcinoma after nephrectomy experienced a clinical benefit with adjuvant sunitinib.Trial registrationClinicalTrials.gov NCT00375674.

Published
2018

5. Loci influencing blood pressure identified using a cardiovascular gene-centric array

Author

Ganesh, Santhi K, Tragante, Vinicius, Guo, Wei, Guo, Yiran, Lanktree, Matthew B, Smith, Erin N, Johnson, Toby, Castillo, Berta Almoguera, Barnard, John, Baumert, Jens, Chang, Yen-Pei Christy, Elbers, Clara C, Farrall, Martin, Fischer, Mary E, Franceschini, Nora, Gaunt, Tom R, Gho, Johannes MIH, Gieger, Christian, Gong, Yan, Isaacs, Aaron, Kleber, Marcus E, Leach, Irene Mateo, McDonough, Caitrin W, Meijs, Matthijs FL, Mellander, Olle, Molony, Cliona M, Nolte, Ilja M, Padmanabhan, Sandosh, Price, Tom S, Rajagopalan, Ramakrishnan, Shaffer, Jonathan, Shah, Sonia, Shen, Haiqing, Soranzo, Nicole, van der Most, Peter J, Van Iperen, Erik PA, Van Setten, Jessic A, Vonk, Judith M, Zhang, Li, Beitelshees, Amber L, Berenson, Gerald S, Bhatt, Deepak L, Boer, Jolanda MA, Boerwinkle, Eric, Burkley, Ben, Burt, Amber, Chakravarti, Aravinda, Chen, Wei, Cooper-DeHoff, Rhonda M, Curtis, Sean P, Dreisbach, Albert, Duggan, David, Ehret, Georg B, Fabsitz, Richard R, Fornage, Myriam, Fox, Ervin, Furlong, Clement E, Gansevoort, Ron T, Hofker, Marten H, Hovingh, G Kees, Kirkland, Susan A, Kottke-Marchant, Kandice, Kutlar, Abdullah, LaCroix, Andrea Z, Langaee, Taimour Y, Li, Yun R, Lin, Honghuang, Liu, Kiang, Maiwald, Steffi, Malik, Rainer, Murugesan, Gurunathan, Newton-Cheh, Christopher, O'Connell, Jeffery R, Onland-Moret, N Charlotte, Ouwehand, Willem H, Palmas, Walter, Penninx, Brenda W, Pepine, Carl J, Pettinger, Mary, Polak, Joseph F, Ramachandran, Vasan S, Ranchalis, Jane, Redline, Susan, Ridker, Paul M, Rose, Lynda M, Scharnag, Hubert, Schork, Nicholas J, Shimbo, Daichi, Shuldiner, Alan R, Srinivasan, Sathanur R, Stolk, Ronald P, Taylor, Herman A, Thorand, Barbara, Trip, Mieke D, van Duijn, Cornelia M, Verschuren, W Monique, Wijmenga, Cisca, Winkelmann, Bernhard R, Wyatt, Sharon, and Young, J Hunter

Subjects
Hypertension, Heart Disease, Human Genome, Genetics, Clinical Research, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Blood Pressure, Cardiovascular Diseases, Chromosome Mapping, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, White People, CARDIOGRAM, METASTROKE, LifeLines Cohort Study, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.

Published
2013

6. Modest association between health literacy and risk for peripheral vascular disease in patients with type 2 diabetes

Author

Chiou, Shang-Jyh, Chang, Yen-Jung, Liao, Kuomeng, and Chen, Chih-Dao

Subjects
Peripheral Vascular Diseases, Diabetes Mellitus, Type 2, Surveys and Questionnaires, Chronic Disease, Public Health, Environmental and Occupational Health, Humans, Health Literacy
Abstract

ObjectiveHealth literacy plays a crucial role in managing chronic health conditions. Previous studies have revealed the positive relationship between health literacy and diabetes knowledge but few studies have focused on peripheral vascular disease (PVD) in diabetes in relation to health literacy in diabetes management. This study investigated the relationship between the risk for PVD and health literacy level with other determining factors among patients with type 2 diabetes.MethodWe conducted a survey on health literacy using the Mandarin Multidimensional Health Literacy Questionnaire in the department of metabolism and endocrine systems at a regional hospital in northern Taiwan from December 2021 to May 2022 and obtained data from the hospital's health information system (HIS) from 2013 to 2020 to identify occurrences of PVD (n = 429). We performed logistic regression analysis to identify the relationship between PVD events and health literacy levels (overall and in five separate subdimensions) adjusted with other variables.ResultsA longer duration of diabetes increased the risk for PVD events (P = 0.044 and 0.028). In terms of health literacy, the overall level was not significant; however, the dimension of higher levels of health literacy in acquiring health information increased the risk for PVD events (P = 0.034). Other variables were not significantly associated with the risk for PVD events.ConclusionThis study examined the risk for PVD events in terms of the duration of diabetes and provided evidence across the range of dimensions of health literacy concerning the ability to control diabetes. Those with a higher level of health literacy may be more aware of their disease situation, seek and cooperate with their healthcare providers earlier, and have more opportunities to be made aware of their health status from regular checkups than those with inadequate health literacy. These results may help providers make available more self-management tools that are adequate and sustainable for diabetes patients with poor health literacy.

Published
2022

7. Risk of Guillain-Barré Syndrome Among Older Adults Receiving Influenza Vaccine in Taiwan

Author

Cheng-Chang, Yen, Kai-Che, Wei, Wen-Hwa, Wang, Yu-Tung, Huang, and Yu-Chia, Chang

Subjects
AIDS Vaccines, Male, SAIDS Vaccines, Taiwan, General Medicine, Guillain-Barre Syndrome, Cross-Sectional Studies, Influenza A Virus, H1N1 Subtype, Influenza Vaccines, Influenza, Human, BCG Vaccine, Respiratory Syncytial Virus Vaccines, Humans, Female, Papillomavirus Vaccines, Diphtheria-Tetanus-Pertussis Vaccine, Measles-Mumps-Rubella Vaccine, Aged
Abstract

ImportanceAlthough influenza vaccination has been associated with Guillain-Barré syndrome (GBS), the findings among studies of older adult populations are inconsistent.ObjectiveTo determine the risk of GBS after influenza vaccination among older adults.Design, Setting, and ParticipantsThis cross-sectional study incorporated a self-controlled case series design. Days 1 to 7, days 1 to 14, and days 1 to 42 after influenza vaccination were identified as risk intervals; days 8 to 180, days 15 to 180, and days 43 to 180 comprised the corresponding control interval. Population-based data were obtained from Taiwan’s National Health Insurance research database between January 1, 2003, and December 31, 2017. Data were analyzed from November 1, 2021, through February 28, 2022. Adults 65 years or older who developed GBS within 180 days after influenza vaccination were enrolled.ExposureGovernment-funded seasonal influenza vaccination.Main Outcomes and MeasuresOnset of GBS during risk intervals after influenza vaccination compared with control intervals using Poisson regression to calculate incidence rate ratio (IRR).ResultsOf 13 482 122 adults aged 65 years or older who received an influenza vaccination, 374 were hospitalized for GBS. The mean (SD) age of the study population was 75.0 (6.1) years; 215 (57.5%) were men and 159 (42.5%) were women. In terms of comorbidities, 33 adults (8.8%) had cancer and 4 (1.1%) had autoimmune diseases. The IRRs for GBS during days 1 to 7, days 1 to 14, and days 1 to 42 were 0.95 (95% CI, 0.55-1.61; P = .84), 0.87 (95% CI, 0.58-1.29; P = .48), and 0.92 (95% CI, 0.72-1.17; P = .49), respectively. No results showed statistical significance. Similarly, no significant differences in IRRs were noted for the overall risk interval (ie, days 1-42) in subgroup analyses pertaining to different age groups (65-74 years [0.93 (95% CI, 0.66-1.31)], 75-84 years [0.85 (95% CI, 0.58-1.26)], and ≥85 years [1.10 (95% CI, 0.57-2.11)]), sex (men, 0.97 [95% CI, 0.71-1.33; P = .87]; women, 0.85 [95% CI, 0.58-1.23; P = .39]), Charlson Comorbidity Index (1.03 [95% CI, 0.77-1.38; P = .84]), or comorbidities (cancer, 0.68 [95% CI, 0.28-1.64; P = .39]; autoimmune disease, 1.10 [95% CI, 0.11-10.53; P = .94]).Conclusions and RelevanceThese findings suggest that influenza vaccination did not increase the risk of GBS among adults aged 65 years or older in Taiwan regardless of postvaccination period or underlying characteristics.

Published
2022

8. Automatic recognition of murmurs of ventricular septal defect using convolutional recurrent neural networks with temporal attentive pooling

Author

Yun-Fan Chang, Jou-Kou Wang, Chui-Hsuan Cheng, Wei-Chien Wang, Yu Tsao, Chang-Yen Tsai, and Kun-Hsi Tsai

Subjects
Adult, Heart Defects, Congenital, Male, congenital, hereditary, and neonatal diseases and abnormalities, Systolic Murmurs, medicine.medical_specialty, Adolescent, Heart malformation, Science, Cardiology, Diseases, Heart Auscultation, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Internal medicine, Diagnosis, Humans, Medicine, cardiovascular diseases, Child, Sound (medical instrument), Multidisciplinary, Heart Murmurs, Artificial neural network, business.industry, Models, Cardiovascular, Health care, Signal Processing, Computer-Assisted, Cardiovascular diseases, Recurrent neural network, Child, Preschool, Heart sounds, Heart murmur, Female, Neural Networks, Computer, medicine.symptom, business, Software
Abstract

Recognizing specific heart sound patterns is important for the diagnosis of structural heart diseases. However, the correct recognition of heart murmur depends largely on clinical experience. Accurately identifying abnormal heart sound patterns is challenging for young and inexperienced clinicians. This study is aimed at the development of a novel algorithm that can automatically recognize systolic murmurs in patients with ventricular septal defects (VSDs). Heart sounds from 51 subjects with VSDs and 25 subjects without a significant heart malformation were obtained in this study. Subsequently, the soundtracks were divided into different training and testing sets to establish the recognition system and evaluate the performance. The automatic murmur recognition system was based on a novel temporal attentive pooling-convolutional recurrent neural network (TAP-CRNN) model. On analyzing the performance using the test data that comprised 178 VSD heart sounds and 60 normal heart sounds, a sensitivity rate of 96.0% was obtained along with a specificity of 96.7%. When analyzing the heart sounds recorded in the second aortic and tricuspid areas, both the sensitivity and specificity were 100%. We demonstrated that the proposed TAP-CRNN system can accurately recognize the systolic murmurs of VSD patients, showing promising potential for the development of software for classifying the heart murmurs of several other structural heart diseases.

Published
2020

9. Effects of heavy metals in acute ischemic stroke patients

Author

Cheng-Chang, Yen, Hsin-Hung, Chen, Yi-Ting, Hsu, Ching-Jiunn, Tseng, and Ching-Huang, Lin

Subjects
Adult, Male, Smoking, Taiwan, Environmental Exposure, Mercury, General Medicine, Middle Aged, Arsenic, Cross-Sectional Studies, Lead, Metals, Heavy, Humans, Female, Aged, Cadmium, Ischemic Stroke
Abstract

Cerebrovascular disease is the second commonest cause of mortality globally and among the commonest causes of disability. However, research executed to probe the heavy metal exposure-stroke incidence relationship is scarce. Accordingly, we executed our study to probe the relationship of heavy metal concentrations (ie, concentrations of lead [Pb], mercury [Hg], cadmium [Cd], and arsenic) in the serum and urine of acute ischemic stroke (AIS) patients with several patient variables.For enrollment, we chose patients who had a first AIS within 7 days after the onset of a stroke. Thus, 33 newly diagnosed patients with AIS were recruited. We determined the aforementioned metals' concentrations by executing inductively coupled plasma mass spectrometry. We also gauged the association between such metal concentrations and patient variables by employing Spearman correlation coefficient. To examine the differences in metal concentrations between the different variables, we implemented an independent Mann-Whitney U test.In our cohort analysis, we noted serum Pb and Cd concentrations to be positively correlated with serum creatinine and hemoglobin. Serum and urine Cd concentrations had a negative correlation with impaired HbA1c in AIS patients. Urine Hg had a positive correlation with C-reactive protein in the participants. Participants who smoked or consumed alcohol had significantly higher Pb and Cd levels in serum than did those who neither smoked nor drank. Patients with AIS who smoked or consumed alcohol had high levels of serum Pb and serum Cd than did those who did not. Patients with AIS who consumed alcohol had significantly higher Pb and Hg urine concentrations than did those who did not.Our study indicated that serum Cd and Pb elevation increased the AIS risk in southern Taiwan patients.

Published
2022

10. [Current Status and Prospects for Information Communication Technology (ICT) in Allied Health Education]

Author

Chang-Yen, Liao and Wen-I, Liu

Subjects
Communication, Allied Health Personnel, Humans, Information Technology, Health Education
Abstract

In this article, technologies that have been widely adopted and used in the field of allied health education in recent years are identified and introduced. These technologies may be distinguished based on education content and approach into the following three categories: online-offline digital education, which uses massive open online courses, CD-ROM, and similar learning tools; mobile learning, which uses mobile phones, tablets, and other devices to connect to the Internet of things; and digital simulation education, which uses virtual reality, virtual patient simulation, serious gaming, and gamification. Preliminary positive findings regarding the effectiveness of using the above technologies have been reported in the literature. Therefore, to better understand the impact of new technology, it is recommended that relevant medical/nursing educators should continue introducing practical courses to evaluate their impact on learning. However, funding limitations and the declining birthrate / population aging are two key threats to education that remain to be effectively addressed and overcome.醫護教育科技現況與展望.本文整理近年來運用於醫護教育領域的相關科技，從中梳理並介紹深具影響力的醫護教育科技。本文依據教育內容和教育方式，將其分為三部分：線上線下數位教育，如大型開放線上課程（massive open online courses）或是使用CD-ROM形式；行動學習（mobile learning or mobile digital education），如使用手機、平板電腦或是其他各式連結物聯網的感測器設備；數位模擬教育，如虛擬實境（virtual reality）、虛擬病人模擬（virtual patient simulation）、遊戲化學習（serious gaming and gamification），已有一些研究應用上述教育科技有正向的成果。為了理解新科技能帶來何種影響，建議相關醫護教育工作者，應該持續導入實務課程，以評估其對於學習的影響。然而，現今仍有二項威脅需克服：財政預算有限與少子高齡化問題。.

Published
2020

11. Novel Mutations in the TMPRSS3 Gene may Contribute to Taiwanese Patients with Nonsyndromic Hearing Loss

Author

Swee-Hee Wong, Jiann-Jou Yang, Yung-Chang Yen, and Shuan-Yow Li

Subjects
Adult, Silent mutation, Adolescent, Xenopus, medicine.medical_treatment, Mutation, Missense, Taiwan, Deafness, medicine.disease_cause, Article, Catalysis, lcsh:Chemistry, Inorganic Chemistry, Serine, Young Adult, xenopus oocyte, medicine, otorhinolaryngologic diseases, Animals, Humans, Point Mutation, Missense mutation, Physical and Theoretical Chemistry, Child, lcsh:QH301-705.5, Molecular Biology, Gene, Spectroscopy, TMPRSS3, hearing loss, Serine protease, Genetics, Mutation, Protease, sGASP, biology, Serine Endopeptidases, Organic Chemistry, Intron, Membrane Proteins, General Medicine, Introns, Neoplasm Proteins, Computer Science Applications, lcsh:Biology (General), lcsh:QD1-999, biology.protein, mutation
Abstract

A previous study indicated that mutations in the transmembrane protease serine 3 (TMPRSS3) gene, which encodes a transmembrane serine protease, cause nonsyndromic hearing loss (NSHL). This was the first description of a serine protease involved in hearing loss (HL). In Taiwan, however, data on the TMPRSS3 gene&rsquo, s association with NSHL is still insufficient. In this study, we described 10 mutations of TMPRSS3 genes found in 14 patients after screening 230 children with NSHL. The prevalence of the TMPRSS3 mutation appeared to be 6.09% (14/230). Of the 10 mutations, three were missense mutations: c.239G&gt, A (p.R80H), c.551T&gt, C (p.L184S), and 1253C&gt, T (p.A418V), three were silent mutations, and four were mutations in introns. To determine the functional importance of TMPRSS3 mutations, we constructed plasmids carrying TMPRSS3 mutations of p.R80H, p.L184S, and p.A418V. TMPRSS3 function can be examined by secretory genetic assay for site-specific proteolysis (sGASP) and Xenopus oocyte expression system. Our results showed that p.R80H, p.L184S, and p.A418V TMPRSS3 mutations gave ratios of 19.4%, 13.2%, and 27.6%, respectively, via the sGASP system. Moreover, these three TMPRSS3 mutations failed to activate the epithelial sodium channel (ENaC) in the Xenopus oocyte expression system. These results indicate that the p.R80H, p.L184S, and p.A418V missense mutations of TMPRSS3 resulted in greatly diminishing the proteolytic activity of TMPRSS3. Our study provides information for understanding the importance of TMPRSS3 in the NSHL of Taiwanese children and provides a novel molecular explanation for the role of TMPRSS3 in HL.

Published
2020
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12. A preliminary study of current situation and competences of doctoral nursing education in Taiwan: A multi-methods research design

Author

Shiau-Ting, Tsai, Mei Chang, Yen, Ya-Chu, Hsiao, Hsiao-Ling, Wang, Mei-Chih, Huang, and Fan-Hao, Chou

Subjects
Adult, Research Design, Taiwan, Humans, Learning, Curriculum, General Medicine, Middle Aged, Education, Nursing, Education, Nursing, Graduate, General Nursing, Education
Abstract

To explore the status and overall competency of Taiwan's doctoral nursing programs.Taiwan has 11 universities offer doctoral degree programs in nursing from 1997 to 2020. As the demand for educators of higher nursing education increases, whether the nursing talent requirements have been satisfactorily fulfilled.A two-stage data collection based on a multi-methods survey was conducted.The first stage from December 2017 to the end of December 2019, involved collecting admission brochures for 12 doctoral nursing programs provided by 11 universities and 14 Internet databases. In the second stage, convenience sampling was performed to recruit 115 graduates of national doctoral nursing programs to collect data through a self-administered questionnaire online survey from July to the end of September 2018.A systematic review of the vision and core competencies of each university revealed a general emphasis on nursing knowledge, research, leadership, international perspective and competence, innovation, social practice and policy. More specifically, universities aim to cultivate five core competencies in students, for example, nursing knowledge, scientific and innovative research capabilities and participation in the formulation and promotion of nursing policies. Of the 115 graduates of national doctoral nursing programs surveyed, the online questionnaire revealed that more than half of the respondents were aged 41-50 years (n = 62, 53.9%), 81.8% occupied a teaching position and most had 2.4-9.8 years of study in the program (mean = 6.09 ± 1.81 years). Respondents who completed a doctoral nursing program in Taiwan could learn orderly teaching, research and leadership capabilities with scored 4.12, 4.11 and 3.65, respectively.The overall orientation of the doctoral nursing programs in Taiwan aligns approximately with global trends in nursing. This study suggests that international and national resources should be incorporated into the cultivation of various competencies and curriculum quality control; moreover, industry, academia and the government should hold regular meetings to formulate suitable evaluation mechanisms.

Published
2022

13. Renal function is associated with 1-month and 1-year mortality in patients with ischemic stroke

Author

I-Kuan Wang, Chung-Hsiang Liu, Tzung-Hai Yen, Jiann-Shing Jeng, Sheng-Feng Sung, Pai-Hao Huang, Jie-Yuan Li, Yu Sun, Cheng-Yu Wei, Li-Ming Lien, I-Ju Tsai, Fung-Chang Sung, Chung Y. Hsu, Chon-Haw Tsai, Wei-Shih Huang, Chung-Ta Lu, Tzung-Chang Tsai, Chun-Hung Tseng, Kang-Hsu Lin, Woei-Cherng Shyu, Yu-Wan Yang, Yen-Liang Liu, Der-Yang Cho, Chun-Chung Chen, Sung-Chun Tang, Li-Kai Tsai, Shin-Joe Yeh, Chih-Hao Chen, Hsin-Hsi Tsai, Han-Jung Chen, Kan Lu, Shih-Pin Hsu, Hung-Chang Kuo, Jung-Chi Tsou, Yan-Tang Wang, Yi-Cheng Tai, Meng-Tsang Hsieh, Po-Chao Liliang, Cheng-Loong Liang, Hao-Kuang Wang, Yu-Tun Tsai, Kuo-Wei Wang, Jui-Sheng Chen, Po-Yuan Chen, Yi-Ching Wang, Chih-Hung Chen, Pi-Shan Sung, Han-Chieh Hsieh, Hui-Chen Su, Hou-Chang Chiu, Wei-Hung Chen, Chyi-Huey Bai, Tzu-Hsuan Huang, Chi-Ieong Lau, Ya-Ying Wu, Hsu-Ling Yeh, Anna Chang, Ching-Huang Lin, Cheng-Chang Yen, Ruey-Tay Lin, Chun-Hung Chen, Gim-Thean Khor, A-Ching Chao, Hsiu-Fen Lin, Poyin Huang, Huey-Juan Lin, Der-Shin Ke, Chia-Yu Chang, Poh-Shiow Yeh, Kao-Chang Lin, Tain-Junn Cheng, Chih-Ho Chou, Chun-Ming Yang, Hsiu-Chu Shen, An-Chih Chen, Shih-Jei Tsai, Tsong-Ming Lu, Sheng-Ling Kung, Mei-Ju Lee, Hsi-Hsien Chou, Wei-Lun Chang, Pai-Yi Chiu, Min-Hsien Hsu, Po-Chi Chan, Chau-Hsiung Pan, Hai-Ming Shoung, Yi-Chen Lo, Fu-Hwa Wang, Wei-Chieh Chang, Ta-Chang Lai, Jiu-Haw Yin, Chung-Jen Wang, Kai-Chen Wang, Li-Mei Chen, Jong-Chyou Denq, Chien-Jung Lu, Cheng-Huai Lin, Chieh-Cheng Huang, Chang-Hsiu Liu, Hoi-Fong Chan, Siu-Pak Lee, Ming-Hui Sun, Li-Ying Ke, Po-Lin Chen, Yu-Shan Lee, Cheung-Ter Ong, Chi-Shun Wu, Yung-Chu Hsu, Yu-Hsiang Su, Ling-Chien Hung, Jiunn-Tay Lee, Jiann-Chyun Lin, Yaw-Don Hsu, Giia-Sheun Peng, Chang-Hung Hsu, Chun-Chieh Lin, Che-Hung Yen, Chun-An Cheng, Yueh-Feng Sung, Yuan-Liang Chen, Ming-Tung Lien, Chung-Hsing Chou, Chia-Chen Liu, Fu-Chi Yang, Yi-Chung Wu, An-Chen Tso, Yu- Hua Lai, Chun-I. Chiang, Chia-Kuang Tsai, Meng-Ta Liu, Ying-Che Lin, Yu-Chuan Hsu, Tsuey-Ru Chiang, Pin-Wen Liao, Mei-Ching Lee, Jen-Tse Chen, Sian-King Lie, Mu-Chien Sun, Pi-Ju Hsiao, Wei-Liang Chen, Ta-Cheng Chen, Chen-Shu Chang, Chien-Hsu Lai, Chieh-Sen Chuang, Yen-Yu Chen, Shinn-Kuang Lin, Yu-Chin Su, Jen-Lun Shiao, Fu-Yi Yang, Chih-Yang Liu, Han-Lin Chiang, Guei-Chiuan Chen, Po-Jen Hsu, Chun-Yuan Chang, I.-sheng Lin, Chung-Hsien Chien, Yang-Chuang Chang, Ping-Kun Chen, Yu-Jen Hsiao, Chen-Wen Fang, Yu-Wei Chen, Kuo-Ying Lee, Yun-Yu Lin, Chen-Hua Li, Hui-Fen Tsai, Chuan-Fa Hsieh, Chih-Dong Yang, Shiumn-Jen Liaw, How-Chin Liao, Shoou-Jeng Yeh, Ling-Li Wu, Liang-Po Hsieh, Yong-Hui Lee, Chung-Wen Chen, Chih-Shan Hsu, Ye-Jian Jhih, Hao-Yu Zhuang, Yan-Hong Pan, Shin-An Shih, Chin-I. Chen, Jia-Ying Sung, Hsing-Yu Weng, Hao-Wen Teng, Jing-Er Lee, Chih-Shan Huang, Shu-Ping Chao, Rey-Yue Yuan, Jau-Jiuan Sheu, Jia-Ming Yu, Chun-Sum Ho, Ting-Chun Lin, Shih-Chieh Yu, Jiunn-Rong Chen, Song-Yen Tsai, Chao-Hsien Hung, Chia Fang Lee, Sheng-Kung Yang, Chih-Lin Chen, Wei Lin, Hung-Pin Tseng, Chin-Hsiung Liu, Chun-Liang Lin, Hung-Chih Lin, Pi-Tzu Chen, Chaur-Jong Hu, Lung Chan, Nai-Fang Chi, Chang-Ming Chern, Chun-Jen Lin, Shuu-Jiun Wang, Li-Chi Hsu, Wen-Jang Wong, I-Hui Lee, Der-Jen Yen, Ching-Piao Tsai, Shang-Yeong Kwan, Bing-Wen Soong, Shih-Pin Chen, Kwong-Kum Liao, Kung-Ping Lin, Chien Chen, Din-E. Shan, Jong-Ling Fuh, Pei-Ning Wang, Yi-Chung Lee, Yu-Hsiang Yu, Hui-Chi Huang, Jui-Yao Tsai, Ming-Hsiu Wu, Szu-Yi Chiang, Chiung-Yao Wang, Ming-Chin Hsu, Chien-Chung Chen, Po-Yen Yeh, Yu-Tai Tsai, Ko-Yi Wang, Tsang-Shan Chen, Cheng-Yang Hsieh, Wei-Fen Chen, Ping-Keung Yip, Vinchi Wang, Kaw-Chen Wang, Chung-Fen Tsai, Chao-Ching Chen, Yi-Chien Liu, Shao-Yuan Chen, Zi-Hao Zhao, Zhi-Peng Wei, Shey-Lin Wu, Ching-Kuan Liu, Ryh-Huei Lin, Ching-Hua Chu, Sui-Hing Yan, Yi-Chun Lin, Pei-Yun Chen, Sheng-Huang Hsiao, Bak-Sau Yip, Pei-Chun Tsai, Ping-Chen Chou, Tsam-Ming Kuo, Yi-Chen Lee, Yi-Pin Chiu, Kun-Chang Tsai, Yi-Sheng Liao, Ming-Jun Tsai, and Hsin-Yi Kao

Subjects
Adult, Male, Stroke registry, medicine.medical_specialty, Time Factors, Adolescent, Taiwan, Renal function, 030204 cardiovascular system & hematology, Kidney, Risk Assessment, Brain Ischemia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Medicine, In patient, Registries, Risk factor, Stroke, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Mortality rate, Middle Aged, Prognosis, medicine.disease, Ischemic stroke, Cardiology, Female, Kidney Diseases, Cardiology and Cardiovascular Medicine, business, 1 year mortality, 030217 neurology & neurosurgery, Glomerular Filtration Rate
Abstract

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Published
2018

14. Determination of the cell tropism of serotype 1 feline infectious peritonitis virus using the spike affinity histochemistry in paraffin‐embedded tissues

Author

Cham, Tat‐Chuan, Chang, Yen‐Chen, Tsai, Pei‐Shiue, Wu, Ching‐Ho, Chen, Hui‐Wen, Jeng, Chian‐Ren, Pang, Victor Fei, and Chang, Hui‐Wen

Subjects
cell tropism, Macrophages, Virus Attachment, Original Articles, spike, Serogroup, N-Acetylneuraminic Acid, Cell Line, Viral Tropism, HEK293 Cells, histochemistry, Virology, Host-Pathogen Interactions, Spike Glycoprotein, Coronavirus, Cats, Animals, Humans, Receptors, Virus, Original Article, Coronavirus, Feline, feline infectious peritonitis virus, Protein Binding
Abstract

Unlike for serotype II feline coronaviruses (FCoV II), the cellular receptor for serotype I FCoV (FCoV I), the most prevalent FCoV serotype, is unknown. To provide a platform for assessing the pattern by which FCoV I attaches to its host receptor(s), HEK293 cell lines that stably express the ectodomains of the spike (S) proteins derived from a FCoV I feline enteric coronavirus strain UU7 (FECV UU7) and a feline infectious peritonitis virus strain UU4 (FIPV UU4) were established. Using the recombinant S proteins as probes to perform S protein affinity histochemistry in paraffin‐embedded tissues, although no tissue or enteric binding of FECV UU7 S protein was detected, it was found that by immunohistochemistry that the tissue distribution of FIPV UU4 S protein‐bound cells correlated with that of FIPV antigen‐positive cells and lesions associated with FIP and that the affinity binding of FIPV UU4 S protein on macrophages was not affected by enzymatic removal of host cell‐surface sialic acid with neuraminidase. These findings suggest that a factor(s) other than sialic acid contribute(s) to the macrophage tropism of FIPV strain UU4. This approach allowed obtaining more information about both virus–host cell interactions and the biological characteristics of the unidentified cellular receptor for FCoV I.

Published
2017

15. Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients

Author

I.-Kuan Wang, Chung-Hsiang Liu, Tzung-Hai Yen, Jiann-Shing Jeng, Shih-Pin Hsu, Chih-Hung Chen, Li-Ming Lien, Ruey-Tay Lin, An-Chih Chen, Huey-Juan Lin, Hsin-Yi Chi, Ta-Chang Lai, Yu Sun, Siu-Pak Lee, Sheng-Feng Sung, Po-Lin Chen, Jiunn-Tay Lee, Tsuey-Ru Chiang, Shinn-Kuang Lin, Chih-Hsin Muo, Henry Ma, Chi-Pang Wen, Fung-Chang Sung, Chung Y. Hsu, Chon-Haw Tsai, Wei-Shih Huang, Chung-Ta Lu, Tzung-Chang Tsai, Chun-Hung Tseng, Kang-Hsu Lin, Woei-Cherng Shyn, Yu-Wan Yang, Yen-Liang Liu, Der-Yang Cho, Chun-Chung Chen, Sung-Chun Tang, Li-Kai Tsai, Shin-Joe Yeh, Han-Jung Chen, Cheng-Sen Chang, Hung-Chang Kuo, Lian-Hui Lee, Huan-Wen Tsui, Jung-Chi Tsou, Yan-Tang Wang, Yi-Cheng Tai, Kun-Chang Tsai, Yen-Wen Chen, Kan Lu, Po-Chao Liliang, Yu-Tun Tsai, Cheng-Loong Liang, Kuo-Wei Wang, Hao-Kuang Wang, Jui-Sheng Chen, Po-Yuan Chen, Cien-Leong Chye, Wei-Jie Tzeng, Pei-Hua Wu, Pi-Shan Sung, Han-Chieh Hsieh, Hui-Chen Su, Hou-Chang Chiu, Wei-Hung Chen, Chyi-Huey Bai, Tzu-Hsuan Huang, Chi-Ieong Lau, Ya-Ying Wu, Hsu-Ling Yeh, Anna Chang, Ching-Huang Lin, Cheng-Chang Yen, Chun-Hung Chen, Gim-Thean Khor, A-Ching Chao, Hsiu-Fen Lin, Poyin Huang, Der-Shin Ke, Chia-Yu Chang, Poh-Shiow Yeh, Kao-Chang Lin, Tain-Junn Cheng, Chih-Ho Chou, Chun-Ming Yang, Hsiu-Chu Shen, Shih-Jei Tsai, Tsong-Ming Lu, Sheng-Ling Kung, Mei-Ju Lee, Hsi-Hsien Chou, Chou-Hsiung Pan, Po-Chi Chan, Min-Hsien Hsu, Wei-Lun Chang, Zhi-Zang Huang, Hai-Ming Shoung, Yi-Chen Lo, Fu-Hwa Wang, Jiu-Haw Yin, Chung-Jen Wang, Kai-Chen Wang, Li-Mei Chen, Jong-Chyou Denq, Chien-Jung Lu, Cheng-Huai Lin, Chieh-Cheng Huang, Chang-Hsiu Liu, Hoi-Fong Chan, Ming-Hui Sun, Li-Ying Ke, Yu-Shan Lee, Cheung-Ter Ong, Chi-Shun Wu, Yung-Chu Hsu, Yu-Hsiang Su, Ling-Chien Hung, Jiann-Chyun Lin, Yaw-Don Hsu, Giia-Sheun Peng, Chang-Hung Hsu, Chun-Chieh Lin, Che-Hung Yen, Chun-An Cheng, Yueh-Feng Sung, Yuan-Liang Chen, Ming-Tung Lien, Chung-Hsing Chou, Chia-Chen Liu, Fu-Chi Yang, Yi-Chung Wu, An-Chen Tso, Yu-Hua Lai, Chun-I Chiang, Chia-Kuang Tsai, Meng-Ta Liu, Ying-Che Lin, Yu-Chuan Hsu, Mei-Ching Lee, Pai-Hao Huang, Sian-King Lie, Pin-Wen Liao, Jen-Tse Chen, Mu-Chien Sun, Tien-Pao Lai, Wei-Liang Chen, Yen-Chun Chen, Ta-Cheng Chen, Wen-Fu Wang, Kwo-Whei Lee, Chen-Shu Chang, Chien-Hsu Lai, Siao-Ya Shih, Chieh-Sen Chuang, Yen-Yu Chen, Chien-Min Chen, Yu-Chin Su, Cheng-Lun Hsiao, Fu-Yi Yang, Chih-Yang Liu, Han-Lin Chiang, Chun-Yuan Chang, I-sheng Lin, Chung-Hsien Chien, Yang-Chuang Chang, Ping-Kun Chen, Pai-Yi Chiu, Yu-Jen Hsiao, Chen-Wen Fang, Yu-Wei Chen, Kuo-Ying Lee, Yun-Yu Lin, Chen-Hua Li, Hui-Fen Tsai, Chuan-Fa Hsieh, Chih-Dong Yang, Shiumn-Jen Liaw, How-Chin Liao, Shoou-Jeng Yeh, Ling-Li Wu, Liang-Po Hsieh, Yong-Hui Lee, Chung-Wen Chen, Chih-Shan Hsu, Ye-Jian Jhih, Hao-Yu Zhuang, Yan-Hong Pan, Shin-An Shih, Chin-I Chen, Jia-Ying Sung, Hsing-Yu Weng, Hao-Wen Teng, Jing-Er Lee, Chih-Shan Huang, Shu-Ping Chao, Rey-Yue Yuan, Jau- Jiuan Sheu, Jia-Ming Yu, Chun-Sum Ho, Ting-Chun Lin, Shih-Chieh Yu, Jiunn-Rong Chen, Song-Yen Tsai, Cheng-Yu Wei, Chao-Nan Yang, Chao-Hsien Hung, Ian Shih, Hung-Pin Tseng, Chin-Hsiung Liu, Chun-Liang Lin, Hung-Chih Lin, Pi-Tzu Chen, Chaur-Jong Hu, Nai-Fang Chi, Lung Chan, Chang-Ming Chern, Chun-Jen Lin, Shuu-Jiun Wang, Li-Chi Hsu, Wen-Jang Wong, I-Hui Lee, Der-Jen Yen, Ching-Piao Tsai, Shang-Yeong Kwan, Bing-Wen Soong, Shih-Pin Chen, Kwong-Kum Liao, Kung-Ping Lin, Chien Chen, Din-E Shan, Jong-Ling Fuh, Pei-Ning Wang, Yi-Chung Lee, Yu-Hsiang Yu, Hui-Chi Huang, Jui-Yao Tsai, Ming-Hsiu Wu, Shi-Cheng Chen, Szu-Yi Chiang, Chiung-Yao Wang, Ming-Chin Hsu, Chien-Chung Chen, Po-Yen Yeh, Yu-Tai Tsai, Ko-Yi Wang, Tsang-Shan Chen, Ping-Keung Yip, Vinchi Wang, Kaw-Chen Wang, Chung-Fen Tsai, Chao-Ching Chen, Chih-Hao Chen, Yi-Chien Liu, Shao-Yuan Chen, Zi-Hao Zhao, Zhi-Peng Wei, Shey-Lin Wu, Ching-Kuan Liu, Ryh-Huei Lin, Ching-Hua Chu, Sui-Hing Yan, Yi-Chun Lin, Pei-Yun Chen, Sheng-Huang Hsiao, Bak-Sau Yip, Pei-Chun Tsai, Ping-Chen Chou, Tsam-Ming Kuo, Yi-Chen Lee, Yi-Pin Chiu, Yi-Sheng Liao, Ming-Jun Tsai, and Hsin-Yi Kao

Subjects
Male, Stroke registry, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Taiwan, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Dialysis patients, Brain Ischemia, 03 medical and health sciences, chemistry.chemical_compound, Patient Admission, 0302 clinical medicine, Renal Dialysis, Risk Factors, Internal medicine, medicine, Humans, Registries, Serum cholesterol, Dialysis, Aged, Proportional Hazards Models, Aged, 80 and over, Cholesterol, business.industry, Mortality rate, Rehabilitation, Middle Aged, Prognosis, Stroke, chemistry, 30 day mortality, Ischemic stroke, Cardiology, Kidney Failure, Chronic, Female, Surgery, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Published
2017

16. Mobile community learning programme's effectiveness in case management for psychiatric nurses: A preliminary randomised controlled trial

Author

Chien Hung Liu, Chang Yen Liao, Pei Ru Chao, Kuo Chung Chu, and Wen-I Liu

Subjects
Adult, medicine.medical_specialty, Taiwan, Psychiatric Nursing, Education, law.invention, Teaching hospital, Education, Distance, 03 medical and health sciences, 0302 clinical medicine, Education, Nursing, Continuing, Randomized controlled trial, Mobile community, law, Surveys and Questionnaires, medicine, Global health, Humans, 030212 general & internal medicine, Psychiatry, Competence (human resources), General Nursing, 030504 nursing, Continuing education, Middle Aged, Case management, Female, 0305 other medical science, Psychology, Case Management, Experience sharing
Abstract

The global health care system has applied case management (CM) as a care delivery service provided by nurses. Nurses require continuing education in CM to enhance their professional knowledge and competence. Mobile communities have been used to promote continuing education for medical professionals. However, limited studies have examined the effectiveness of such learning programmes in CM for psychiatric nurses.To evaluate the effectiveness of a mobile community learning (MCL) programme in CM for psychiatric nurses.This study used an experimental two-group pre- and post-test design.Psychiatric nurses employed in a psychiatric teaching hospital situated in northern Taiwan were recruited.Nurses were randomly allocated to the experimental or comparison group. The former participated in the learning intervention in CM. The CM knowledge index and a competence scale were used to determine outcomes. Pre-tests and 2-month post-tests were conducted. The MCL programme comprised five simulated learning modules, self-assessment questions, learning cases, learning resources and experience sharing. A two-way repeated-measures analysis of variance was performed to evaluate the effect of the intervention on target outcomes.The questionnaires were completed by 48 participants. The two groups possessed high homogeneity with regard to characteristics and pre-test outcomes. Differences between the two groups regarding CM knowledge (F = 22.99, p .01) and competence (F = 6.33, p = .015) were significant. The programme had a positive benefit on the learning experience in the experimental group; the mean satisfaction score for the programme reached 4.27 (range, 1-5).MCL programmes for psychiatric nurses can effectively enhance CM knowledge and competence. However, these methods cannot completely replace the continuing education approach for achieving CM competence.

Published
2019

17. Evolutionary histories of coxsackievirus B5 and swine vesicular disease virus reconstructed by phylodynamic and sequence variation analyses

Author

Bao-Chen Chen, Hui-Wen Huang, Yu-Chang Tyan, Chu-Hsiang Pan, Yao-Shen Chen, Chien-Ching Lin, Chih-Hung Chuang, Hsiao-Fen Lee, Po-Liang Lu, Tsi-Shu Huang, Pei-Huan Chu, Chu-Feng Wang, Yung-Chang Yen, Li-Chiu Chou, Yong-Ying Shi, Yi-Ying Lin, Pei-Yu Chu, and Hui-Ju Su

Subjects
0301 basic medicine, China, Genotype, Swine, Sequence analysis, viruses, Coxsackievirus Infections, lcsh:Medicine, Host tropism, Coxsackievirus, Evolution, Molecular, Viral Proteins, 03 medical and health sciences, Spatio-Temporal Analysis, Phylogenetics, Genetic variation, Animals, Cluster Analysis, Humans, lcsh:Science, Gene, Phylogeny, Swine Diseases, Genetics, Multidisciplinary, biology, lcsh:R, Genetic Variation, DNA-Directed RNA Polymerases, Sequence Analysis, DNA, biology.organism_classification, Enterovirus B, Human, Swine Vesicular Disease Virus, 030104 developmental biology, Italy, Epistasis, Capsid Proteins, lcsh:Q
Abstract

Coxsackievirus (CV)-B5 is a common human enterovirus reported worldwide; swine vesicular disease virus (SVDV) is a porcine variant of CV-B5. To clarify the transmission dynamics and molecular basis of host switching between CV-B5 and SVDV, we analysed and compared the VP1 and partial 3Dpol gene regions of these two viruses. Spatiotemporal dynamics of viral transmission were estimated using a Bayesian statistical inference framework. The detected selection events were used to analyse the key molecules associated with host switching. Analyses of VP1 sequences revealed six CV-B5 genotypes (A1–A4 and B1–B2) and three SVDV genotypes (I–III). Analyses of partial 3Dpol revealed five clusters (A–E). The genotypes evolved sequentially over different periods, albeit with some overlap. The major hub of CV-B5 transmission was in China whereas the major hubs of SVDV transmission were in Italy. Network analysis based on deduced amino acid sequences showed a diverse extension of the VP1 structural protein, whereas most sequences were clustered into two haplotypes in the partial 3Dpol region. Residue 178 of VP1 showed four epistatic interactions with residues known to play essential roles in viral host tropism, cell entry, and viral decoating.

Published
2018

18. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author

Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'an, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O'Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, McArdle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N. 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T., Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R. G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Anders, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcus, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Panos, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Janos, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charles, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Maris, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. 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Amsterdam institute for Infection and Immunity, Nephrology, Epidemiologie, RS: CARIM School for Cardiovascular Diseases, Epidemiology, Medical Microbiology & Infectious Diseases, Radiology & Nuclear Medicine, Cardiology, Internal Medicine, Clinical Genetics, Erasmus MC other, Obstetrics & Gynecology, International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Zhao, Jing Hua [0000-0003-4930-3582], Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Khaw, Kay-Tee [0000-0002-8802-2903], Danesh, John [0000-0003-1158-6791], Soranzo, Nicole [0000-0003-1095-3852], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Clinical Pharmacology and The Genome Centre, Queen Mary University of London (QMUL), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Center for Human Genetic Research, Massachusetts General Hospital [Boston], Program in Medical and Population Genetics, Harvard University-Massachusetts Institute of Technology (MIT), Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'An, Arora, Pankaj, Dehghan, Abba, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O'Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, Mcardle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N. M., Lawlor, Debbie A., Beilby, John P., Lawrence, Robert W., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Dreisbach, Albert W., Li, Yali, Hunter Young, J., Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthia, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johanne, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inê, Khaw, Kay-Tee, Weder, Alan B., Hunt, Steven C., Sun, Yan V., Bergman, Richard N., Collins, Francis S., Bonnycastle, Lori L., Scott, Laura J., Stringham, Heather M., Peltonen, Leena, Perola, Marku, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A., Wang, Thomas J., Burton, Paul R., Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K., Rudock, Megan E., Heckbert, Susan R., Smith, Nicholas L., Wiggins, Kerri L., Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margu, Kinra, Sanjay, Prabhakaran, Dorairaj, Tripathy, Vikal, Langefeld, Carl D., Rosengren, Annika, Thelle, Dag S., Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, Mckenzie, Colin A., Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thoma, Wichmann, H. -Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, Jame, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, O'Donnell, Christopher J., Schwartz, Stephen M., Arfan Ikram, M., Longstreth Jr., W. T., Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R. G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Ander, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcu, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Pano, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Jano, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charle, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Mari, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rotter, Jerome I., Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C. M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang, H, Knowles, J, Hlatky, M, Fortmann, S, Assimes, Tl, Quertermous, T, Go, A, Iribarren, C, Absher, D, Risch, N, Meyers, R, Sidney, S, Ziegler, A, Schillert, A, Bickel, C, Sinning, C, Rupprecht, Hj, Lackner, K, Wild, P, Schnabel, R, Blankenberg, S, Zeller, T, Münzel, T, Perret, C, Cambien, F, Tiret, L, Nicaud, V, Proust, C, Dehghan, A, Hofman, A, Uitterlinden, A, van Duijn, C, Levy, D, Whitteman, J, Cupples, La, Demissie-Banjaw, S, Ramachandran, V, Smith, A, Gudnason, V, Boerwinkle, E, Folsom, A, Morrison, A, Psaty, Bm, Chen, Iy, Rotter, Ji, Bis, J, Volcik, K, Rice, K, Taylor, Kd, Marciante, K, Smith, N, Glazer, N, Heckbert, S, Harris, T, Lumley, T, Kong, A, Thorleifsson, G, Thorgeirsson, G, Holm, H, Gulcher, Jr, Stefansson, K, Andersen, K, Gretarsdottir, S, Thorsteinsdottir, U, Preuss, M, Schreiber, S, Meitinger, T, König, Ir, Lieb, W, Hengstenberg, C, Schunkert, H, Erdmann, J, Fisher, M, Grosshennig, A, Medack, A, Stark, K, Linsel-Nitschke, P, Bruse, P, Aherrahrou, Z, Peters, A, Loley, C, Willenborg, C, Nahrstedt, J, Freyer, J, Gulde, S, Doering, A, Meisinger, C, Wichmann, He, Klopp, N, Illig, T, Meinitzer, A, Tomaschitz, A, Halperin, E, Dobnig, H, Scharnagl, H, Kleber, M, Laaksonen, R, Pilz, S, Grammer, Tb, Stojakovic, T, Renner, W, März, W, Böhm, Bo, Winkelmann, Br, Winkler, K, Hoffmann, M, O'Donnell, Cj, Voight, Bf, Altshuler, D, Siscovick, D, Musunuru, K, Peltonen, L, Barbalic, M, Melander, O, Elosua, R, Kathiresan, S, Schwartz, Sm, Salomaa, V, Guiducci, C, Burtt, N, Gabriel, Sb, Stewart, Af, Wells, Ga, Chen, L, Jarinova, O, Roberts, R, Mcpherson, R, Dandona, S, Pichard, Ad, Rader, Dj, Devaney, J, Lindsay, Jm, Kent, Km, Qu, L, Satler, L, Burnett, M, Li, M, Reilly, Mp, Wilensky, R, Waksman, R, Epstein, S, Mattha, W, Knouf, Cw, Waterworth, Dm, Hakonarson, Hh, Walker, M, Mooser, V, Hall, A, Balmforth, Aj, Wright, Bj, Nelson, C, Thompson, Jr, Samani, Nj, Braund, P, Ball, Sg, Smith, Nl, Felix, Jf, Morrison, Ac, Demissie, S, Glazer, Nl, Loehr, Lr, Rosamond, Wd, Rivadeneira, F, Bis, Jc, Folsom, Ar, Benjamin, E, Aulchenko, Y, Haritunians, T, Couper, D, Murabito, J, Wang, Ya, Stricker, B, Gottdiener, J, Chang, Pp, Wang, Tj, Rice, Km, Heckbert, Sr, Fox, Er, Uitterlinden, Ag, Willerson, Jt, van Duijn, Cm, Witteman, Jc, Vasan, R, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Parsa, A, Gao, X, Yang, Q, Smith, Av, O'Connell, Jr, Schmidt, H, Tanaka, T, Isaacs, A, Ketkar, S, Hwang, Sj, Johnson, A, Teumer, A, Paré, G, Atkinson, Ej, Lohman, K, Cornelis, Mc, Probst-Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Aspelund, T, Eiriksdottir, G, Launer, Lj, Harris, Tb, Rampersaud, E, Mitchell, Bd, Arking, De, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, Francesco, Metter, J, de Boer, J, Zillikens, Mc, Oostra, Ba, Feitosa, M, Province, M, de Andrade, M, Turne, St, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, A, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Liu, Y, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Prokopenko, I, Wang, W, Shuldiner, Ar, Coresh, J, Schmidt, R, Ferrucci, L, Shlipak, Mg, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Felix, Sb, Watzinger, N, Larson, Mg, Homuth, G, Aragam, J, Dörr, M, Zweiker, R, Lind, L, Rodeheffer, Rj, Greiser, Kh, Deckers, Jw, Stritzke, J, Lackner, Kj, Ingelsson, E, Kullo, I, Haerting, J, Stricker, Bh, Reffelmann, T, Redfield, Mm, Werdan, K, Mitchell, Gf, Arnett, D, Blettner, M, Friedrich, N, Benjamin, Ej, Chambers, Jc, Zhang, W, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Davey Smith, G, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, T, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, Homan van der Heide, Jj, Hepkema, Bg, Hernandez-Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Munroe, Pb, Nordfors, L, Penninx, Bw, Perucha, E, Pouta, A, Roderick, Pj, Ruokonen, A, Sanna, S, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliot, P, and Kooner, Js.

Subjects
novel loci, Kidney Disease, Polymorphism, Single Nucleotide/*genetics, [SDV]Life Sciences [q-bio], left ventricular wall thickness, LOCI, Genome-wide association study, Blood Pressure, Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, RELEVANCE, Africa/ethnology, Cardiovascular Disease, genetics, Kidney Diseases/genetics, Stroke, genome wide association study, POPULATION, ta118, Blood pressure, hypertension, stroke, coronary artery disease, ddc:616, 0303 health sciences, education.field_of_study, Asia/ethnology, Multidisciplinary, Coronary Artery Disease/genetics, COMMON VARIANTS, Genetic Predisposition to Disease/*genetics, 3. Good health, Europe, Cardiovascular Diseases, Hypertension, Cardiology, Kidney Diseases, HEALTH, Human, medicine.medical_specialty, Asia, Population, Renal function, Polymorphism, Single Nucleotide, Europe/ethnology, Article, CLONING, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Stroke/genetics, Internal medicine, medicine, Humans, Cardiovascular Diseases/*genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, METAANALYSIS, 030304 developmental biology, RECEPTOR, genes, blood pressure, cardiovascular disease risk, medicine.disease, Africa, Blood Pressure/*genetics/physiology, Hypertension/genetics, Kidney disease, Genome-Wide Association Study
Abstract

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. ispartof: Nature vol:478 issue:7367 pages:103-109 ispartof: location:England status: published

Published
2011

19. An Application of NGS for

Author

Hsuan-An, Su, Shuan-Yow, Li, Jiann-Jou, Yang, and Yung-Chang, Yen

Subjects
Adult, Male, JOAG, Adolescent, RNA Splicing, Taiwan, WDR36, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, Middle Aged, Polymorphism, Single Nucleotide, polymorphism, Young Adult, mutation, glaucoma, Asian People, Haplotypes, Mutation, Humans, Female, Genetic Testing, Age of Onset, Eye Proteins, Glaucoma, Open-Angle, Research Paper
Abstract

Primary open-angle glaucoma (POAG) is one of the most important disease in ophthalmology with high prevalence and risk of irreversible blindness. If diagnosed before the age of 35, it is usually categorized as juvenile open-angle glaucoma (JOAG). The WDR36 gene is reckoned as one of the major causative genes of POAG, and had been studied to be related to the pathogenesis of POAG in the literature. We have selected 61 JOAG patients and 61 JOAG-free individuals, and by next-generation sequencing method, the WDR36 gene of the subjects were analyzed. We identified 26 variations exclusively in JOAG group. Among these 26 variations, there were 3 noteworthy variations. First, a novel variation c.460-650A>G was found in our study which might cause premature termination of splicing of the conserved domain in WDR36; second, c.1494+1111G>T (rs13178997) had significantly different frequency in our JOAG patients compared to the reference frequency on NCBI; third, a variation c.710+30C>T (rs10038177) was found in our study, which had already been reported to be related to high-pressure glaucoma. We offer the profile of WDR36 in JOAG in Taiwan population, and we suggest that WDR36 gene is involved in the pathogenesis of JOAG as a subordinate modifier gene.

Published
2017

20. Mechanism of Two Novel Human GJC3 Missense Mutations in Causing Non-Syndromic Hearing Loss

Author

Wei-Guang Liang, Yung-Chang Yen, Shuan-Yow Li, Jiann-Jou Yang, Ching-Chyuan Su, and Jhih-Hao Nian

Subjects
Databases, Factual, Hearing loss, Molecular Sequence Data, Mutant, Cell, Mutation, Missense, Biophysics, Nerve Tissue Proteins, Biology, medicine.disease_cause, Biochemistry, Connexins, Mutant protein, medicine, Humans, Missense mutation, Amino Acid Sequence, Cloning, Molecular, Hearing Loss, Gene, Mutation, Computational Biology, Cell Biology, General Medicine, Molecular biology, Protein Structure, Tertiary, medicine.anatomical_structure, medicine.symptom, Sequence Alignment, Intracellular, HeLa Cells
Abstract

Connexins (CXs), as a component of gap junction channel, are homologous four transmembrane-domain proteins, with numerous studies confirming their auditory functions. Among a cohort of patients having incurred non-syndromic hearing loss, we identified two novel missense mutations, p.R15G and p.L23H, in the GJC3 gene encoding CX30.2/CX31.3, as causally related to hearing loss in previous study. However, the functional alteration of CX30.2/CX31.3 caused by the mutant GJC3 gene remains unknown. In this study, we compared the intracellular distribution of mutant CX30.2/CX31.3 (p.R15G and p.L23H) with the wild-type (WT) protein in HeLa cells and the effect of the mutant protein had on those cells. Analytical results indicated that p.R15G and p.L23H mutant exhibited continuous staining along apposed cell membranes in the fluorescent localization assay, which is the same with the WT. Moreover, ATP release (hemichannel function) is less in HeLa cells carrying mutant GJC3 genes than those of WT expressing cells. We believe that although p.R15G and p.L23H mutants do not decrease the trafficking of CX proteins, mutations in GJC3 genes result in a loss of hemichannel function of CX30.2/CX31.3 protein, possibly causing hearing loss. Results of this study provide a novel molecular explanation for the role of GJC3 in hearing loss.

Published
2012

21. Relapse and Long-Acting Injectable Risperidone: A 1-Year Mirror Image Study with a National Claims Database in Taiwan

Author

Kuan-Pin Su, Hui Chih Chang, Chao Hsiun Tang, Feng Chang Yen, and Shih-Jen Tsai

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Databases, Factual, National Health Programs, Cost-Benefit Analysis, Taiwan, MEDLINE, Injections, Intramuscular, Young Adult, Statistical significance, Outcome Assessment, Health Care, Secondary Prevention, Humans, Medicine, National Health Insurance, Young adult, Psychiatry, Aged, relapse, Risperidone, business.industry, Health Policy, Public Health, Environmental and Occupational Health, Length of Stay, Middle Aged, medicine.disease, National health insurance, Schizophrenia, Cohort, risperidone long-acting injection, Female, business, Antipsychotic Agents, Follow-Up Studies, Diagnosis of schizophrenia, medicine.drug
Abstract

Objectives: The development of long-acting, injectable atypical antipsychotics has provided a new paradigm for schizophrenia treatment. The study was designed to assess whether a risperidone long-acting injection (RLAI) is associated with reduced relapses and service utilization in the real world. Methods: The Psychiatric Inpatients Medical Claims dataset was used for the analysis. It is a longitudinal dataset that includes the National Health Insurance claims of service uses by a cohort of mentally ill patients. The inclusion criteria for this analysis were patients who: 1) had available information for at least 12 months after the first dose of RLAI; 2) had a primary diagnosis of schizophrenia; and 3) were regularly treated with RLAI for at least 1 year. Patients who accumulatively received at least 75-mg RLAI per 3-month period were considered to be undergoing regular treatment. Wilcoxon signed rank tests were performed to compare differences in numbers of acute admissions, hospital days, emergency room visits, and relapses between the pre- and post-RLAI periods in this 1-year mirror-image study. Results: In total, 108 patients were eligible for analysis. Significant reductions in the total annual numbers of acute hospital admissions by 55% (80 vs. 36, P = 0.0003), hospital days by 48% (4106 vs. 2126, P = 0.0021), and relapses by 54% (115 vs. 53, P = 0.0005) were observed. A reduction of emergency room visits was also observed, but did not reach statistical significance (55 vs. 25, P = 0.1255). Conclusions: This 1-year mirror-image analysis with claims-based data demonstrated that RLAI treatment was associated with reductions in relapses and hospital service utilization.

Published
2009

22. Haplotype analysis of single nucleotide polymorphisms in the vascular endothelial growth factor (VEGFA) gene and antidepressant treatment response in major depressive disorder

Author

Tai-Jui Chen, Shih-Jen Tsai, Chen-Jee Hong, Ying-Jay Liou, Feng-Chang Yen, Younger W.-Y. Yu, Mao-Liang Chen, and Sheue-Jane Hou

Subjects
Adult, Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Time Factors, Genotype, Serotonin reuptake inhibitor, Citalopram, Pharmacology, Polymorphism, Single Nucleotide, Young Adult, chemistry.chemical_compound, Gene Frequency, Fluoxetine, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Biological Psychiatry, Depressive Disorder, Major, Middle Aged, medicine.disease, Antidepressive Agents, Vascular endothelial growth factor, Psychiatry and Mental health, Vascular endothelial growth factor A, Endocrinology, chemistry, Pharmacogenetics, Major depressive disorder, Antidepressant, Female, Psychology, medicine.drug
Abstract

Vascular endothelial growth factor (VEGF) has been implicated in neurotrophy and neurogenesis, which play a pivotal role in brain development and may be involved in antidepressant therapeutic mechanisms. Recent animal studies demonstrate that VEGF levels are increased by several antidepressants, including selective serotonin reuptake inhibitors, and that VEGF signalling is required for antidepressant-induced behavioural response. We hypothesized that common genetic variants in the VEGF gene (official gene name: VEGFA) may be associated with the therapeutic response to antidepressants in major depressive disorders (MDD). Seven VEGFA polymorphisms were genotyped in 351 patients with MDD who were treated with selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressants and who were were studied in a therapeutic evaluation for at least 4 weeks. Of the 351 patients, 158 completed an 8-week therapeutic evaluation. No significant association with either 4-week or 8-week antidepressant therapeutic effect was shown in the alleles and genotypes of single loci, or haplotypes from two blocks constructed from these polymorphisms. Our findings suggested that VEGFA genetic variants do not play a major role in the response to selective serotonin reuptake inhibitors.

Published
2009

23. The Myofascial Trigger Point Region

Author

Shu Min Chen, Yueh-Ling Hsieh, Jo Tong Chen, Wei Chang Yen, Ta Shen Kuan, and Chang-Zern Hong

Subjects
Adult, Male, Pain Threshold, Upper trapezius, medicine.medical_specialty, Pressure pain, Physical Therapy, Sports Therapy and Rehabilitation, Electromyography, Irritability, Motor Endplate, Correlation, Physical medicine and rehabilitation, Threshold of pain, medicine, Humans, Muscle, Skeletal, Myofascial Pain Syndromes, Myofascial trigger point, medicine.diagnostic_test, business.industry, Rehabilitation, Middle Aged, medicine.disease, Upper trapezius muscle, Female, medicine.symptom, business
Abstract

Kuan T-S, Hsieh Y-L, Chen S-M, Chen J-T, Yen W-C, Hong C-Z: The myofascial trigger point region: correlation between the degree of irritability and the prevalence of endplate noise. Am J Phys Med Rehabil 2007;86:183‐189. Objective: This study was designed to investigate the correlation between the irritability of the myofascial trigger point (MTrP) and the prevalence of endplate noise (EPN) in the MTrP region of human skeletal muscle. Design: Twenty normal subjects with latent MTrPs and 12 patients with active MTrPs in the upper trapezius muscles were recruited for this study. The patients reported the subjective pain intensity of the active MTrP (0‐10). The MTrP and an adjacent non-MTrP site were confirmed and marked for the measurement of pressure pain threshold (with a pressure algometer) and the prevalence of EPN (with electromyographic recordings). Results: The prevalence of EPN in the MTrP regions was significantly higher (P 0.01) in the active MTrPs than in the latent ones. However, no EPN could be found in the non-MTrP region near either the active or the latent MTrPs. The pain intensity and the pressure pain threshold were highly correlated with the prevalence of EPN in the MTrP region (r 0.742 and 0.716, respectively). Conclusions: The irritability of an MTrP is highly correlated with the prevalence of EPN in the MTrP region of the upper trapezius muscle. The assessment of EPN prevalence in an MTrP region may be applied to evaluate the irritability of that MTrP.

Published
2007

24. Cognitive Severity-Specific Neuronal Degenerative Network in Charcoal Burning Suicide-Related Carbon Monoxide Intoxication

Author

Chen, Nai-Ching, Huang, Chi-Wei, Huang, Shu-Hua, Chang, Wen-Neng, Chang, Ya-Ting, Lui, Chun-Chung, Lin, Pin-Hsuan, Lee, Chen-Chang, Chang, Yen-Hsiang, and Chang, Chiung-Chih

Subjects
Adult, Male, Carbon Monoxide, Taiwan, Observational Study, Brain, Prefrontal Cortex, Middle Aged, Magnetic Resonance Imaging, Severity of Illness Index, White Matter, Article, Suicide, Charcoal, Positron-Emission Tomography, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Anisotropy, Humans, Female, Frontotemporal Lobar Degeneration, Cognition Disorders
Abstract

Supplemental Digital Content is available in the text, While carbon monoxide (CO) intoxication often triggers multiple intraneuronal immune- or inflammatory-related cascades, it is not known whether the pathological processes within the affected regions evolve equally in the long term. To understand the neurodegenerative networks, we examined 49 patients with a clinical diagnosis of CO intoxication related to charcoal burning suicide at the chronic stage and compared them with 15 age- and sex-matched controls. Reconstructions of degenerative networks were performed using T1 magnetic resonance imaging, diffusion-tensor imaging, and fluorodeoxyglucose positron emission tomography (PET). Tract-specific fractional anisotropy (FA) quantification of 11 association fibers was performed while the clinical significance of the reconstructed structural or functional networks was determined by correlating them with the cognitive parameters. Compared with the controls, the patients had frontotemporal gray matter (GM) atrophy, diffuse white matter (WM) FA decrement, and axial diffusivity (AD) increment. The patients were further stratified into 3 groups based on the cognitive severities. The spatial extents within the frontal-insular-caudate GM as well as the prefrontal WM AD increment regions determined the cognitive severities among 3 groups. Meanwhile, the prefrontal WM FA values and PET signals also correlated significantly with the patient's Mini-Mental State Examination score. Frontal hypometabolic patterns in PET analysis, even after adjusted for GM volume, were highly coherent to the GM atrophic regions, suggesting structural basis of functional alterations. Among the calculated major association bundles, only the anterior thalamic radiation FA values correlated significantly with all chosen cognitive scores. Our findings suggest that fronto-insular-caudate areas represent target degenerative network in CO intoxication. The topography that occurred at a cognitive severity-specific level at the chronic phase suggested the clinical roles of frontal areas. Although changes in FA are also diffusely distributed, different regional changes in AD suggested unequal long-term compensatory capacities among WM bundles. As such, the affected WM regions showing irreversible changes may exert adverse impacts to the interconnected GM structures.

Published
2015

25. RISK OF RETINAL VEIN OCCLUSION IN PATIENTS WITH PSORIASIS: A Population-Based Cohort Study

Author

Shih-Feng Weng, Yung Chang Yen, Yong-Song Lin, and Feng Jie Lai

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Databases, Factual, National Health Programs, Population, Taiwan, Risk Factors, Psoriasis, Internal medicine, Retinal Vein Occlusion, medicine, Humans, Risk factor, education, Child, Aged, Proportional Hazards Models, Retrospective Studies, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Age Factors, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Confidence interval, Surgery, Ophthalmology, Child, Preschool, Female, business, Cohort study
Abstract

Purpose To investigate the risk of developing retinal vein occlusion (RVO) in patients with psoriasis. Methods In this retrospective population-based cohort study, 30,198 patients with psoriasis (Psoriasis((+)) group) and 30,198 controls without psoriasis (Psoriasis((−)) group) between 2001 and 2006 from the Taiwan National Health Insurance Research Database were selected. Results The incidence of RVO was 1.46 times higher in the Psoriasis((+)) group than in the Psoriasis((−)) group (3.61 vs. 2.47/10,000 person-years) (adjusted hazard ratio = 1.50; 95% confidence interval = 1.07-2.10) calculated using Cox proportional hazard regression. Age was an independent risk factor for RVO (adjusted hazard ratio: 11.9 for patients 65 years or older vs. 1.00 for those 0-49 years old). In the 65 years or older Psoriasis((+)) group, the incidence of developing RVO was 1.97 times higher (95% confidence interval = 1.19-3.26) than in the 65 years or older Psoriasis((−)) group. In Psoriasis((+)) women, the incidence of developing RVO was 1.82 times higher (95% = 1.05-3.14) than in Psoriasis((−)) women. For the subgroup with comorbid hypertension, the incidence of developing RVO was 2.07 times higher (95% confidence interval = 1.22-3.50) in the Psoriasis((+)) group than in the Psoriasis((−)) group. Conclusion Psoriasis was significantly associated with a higher risk of developing RVO.

Published
2015

26. Higher risk of developing sudden sensorineural hearing loss in patients with chronic otitis media

Author

Yung-Song Lin, Shih-Feng Weng, Yung-Chang Yen, and Charlene Lin

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Hearing loss, Hearing Loss, Sensorineural, Taiwan, Rate ratio, Risk Factors, Internal medicine, medicine, Humans, Child, Aged, Retrospective Studies, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Case-control study, Infant, Retrospective cohort study, Hearing Loss, Sudden, Middle Aged, medicine.disease, Surgery, Otitis Media, Otorhinolaryngology, Case-Control Studies, Child, Preschool, Cohort, Chronic Disease, Sensorineural hearing loss, Female, medicine.symptom, business
Abstract

Importance Several sources have suggested an association between chronic sensory hearing impairment and chronic otitis media (COM). However, to our knowledge, no studies have evaluated the risk of sudden sensorineural hearing loss (SSNHL) in patients with COM (COM-positive). Objective To examine the risk of developing SSNHL in COM-positive patients. Design, Setting, and Participants This was a retrospective cohort study; we compared 10 248 patients with newly diagnosed COM from January 1, 2001, through December 31, 2008, with 30 744 age- and sex-matched controls using data from Taiwan’s National Health Insurance Research Database. Methods We followed each patient and evaluated the incidence of SSNHL. Main Outcomes and Measures The incidence of SSNHL at the end of 2011. Results The incidence of SSNHL was 3 times higher in the COM-positive cohort than in the COM-negative cohort (14.47 vs 4.83 per 10 000 person-years). Cox proportional hazard regressions showed that the adjusted hazard ratio (AHR) was 3.02 (95% CI, 2.30-3.98). A stratified analysis showed that the highest risk of developing SSNHL was in the first follow-up year (incidence rate ratio [IRR], 3.87; 95% CI, 1.93-7.79). Thereafter, the risk declined during years 1 to 5 and then peaked (IRR, 3.01; 95% CI, 1.89-4.79). Patients who needed surgery had a higher incidence of SSNHL (AHR, 2.69; 95% CI, 1.62-4.48) compared with patients who needed only medication and observation. Conclusions and Relevance Chronic otitis media was significantly associated with a higher risk of developing SSNHL.

Published
2015

27. Risk of sudden sensorineural hearing loss in patients with psoriasis: a retrospective cohort study

Author

Feng Jie Lai, Yung Chang Yen, Yong-Song Lin, and Shih-Feng Weng

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Hearing loss, Hearing Loss, Sensorineural, Population, Taiwan, Dermatology, Disease, Comorbidity, Audiology, Young Adult, Psoriasis, medicine, Humans, education, Child, Aged, Retrospective Studies, Autoimmune disease, education.field_of_study, business.industry, Incidence, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Child, Preschool, Sensorineural hearing loss, Female, medicine.symptom, business
Abstract

Psoriasis, a common immune-mediated disease, affects approximately 2% of the population worldwide. Sudden sensorineural hearing loss (SSNHL) might be a manifestation of systemic vascular involvement in autoimmune disease. However, to the best of our knowledge, there is no systematic English-language examination of the risk of SSNHL in patients with psoriasis.We tested the hypothesis that psoriasis is a risk factor for developing SSNHL.Using Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study to compare patients diagnosed with psoriasis from January 1, 2001 through December 31, 2006 (n=28,817) with gender-, age-, and comorbidities-matched controls (n=28,817). We followed each patient until the end of 2011 and evaluated the incidence of SSNHL for at least 6 years after the initial psoriasis diagnosis.The incidence of SSNHL was 1.51 times higher in the psoriasis cohort than in the control cohort (7.12 vs 4.73 per 10,000 person-years). Using Cox proportional hazard regressions, the adjusted hazard ratio (AHR) was 1.51 (95% confidence interval [CI] 1.18-1.93). Comorbid hypertension was an independent risk factor for SSNHL (AHR 1.49; 95% CI 1.05-2.13). However, the incidence rate ratios (IRRs) for each comorbidity subgroup in the psoriasis and control cohorts were not significantly different.Psoriasis was significantly associated with a higher risk of developing SSNHL. We suggest that physicians advise patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL.

Published
2015

28. Genetic studies of body mass index yield new insights for obesity biology

Author

Locke, Adam E, Kahali, Bratati, Croteau-Chonka, Damien C, Doney, Alex S F, He, Bing, Heikkilä, Outi, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Eklund, Niina, Saraheimo, Markku, Sarti, Cinzia, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Estrada, Karol, Wadén, Johan, Gill, Geoffrey V, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Eury, Elodie, Ladenvall, Claes, Alhenc-Gelas, François, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Folkersen, Lasse, Möllsten, Anna, Cimponeriu, Dan, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Fraser, Ross M, Colhoun, Helen M, Panduru, Nicolae Mircea, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Garcia, Melissa E, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Geller, Frank, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L, Mora, Samia, Giedraitis, Vilmantas, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Chang, Hsing-Y, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Gigante, Bruna, Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Freitag, Daniel F, Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U, Esko, Tonu, Go, Alan S, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Golay, Alain, Mihailov, Evelin, Montasser, May E, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Goodall, Alison H, Service, Susan K, Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Thorleifsson, Gudmar, Gordon, Scott D, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Gorski, Mathias, Been, Latonya F, Bolton, Jennifer L, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doring, Angela, Elliott, Paul, Grabe, Hans-Jörgen, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hallmans, Göran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John J P, Khaw, Kay-Tee, Kim, Eric, Grammer, Tanja B, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J F, Mach, François, McArdle, Wendy L, Gräßler, Jürgen, Meisinger, Christa, Mitchell, Braxton D, Muller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V M, Nsubuga, Rebecca N, Olafsson, Isleifur, Ong, Ken K, Palotie, Aarno, Grönberg, Henrik, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J, Reilly, Muredach P, Ridker, Paul M, Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Fall, Tove, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J, Tiret, Laurence, Uitterlinden, Andre G, van Pelt, L Joost, Vedantam, Sailaja, Gusto, Gaëlle, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H, Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F, Young, Elizabeth H, Zhao, Jing Hua, Adair, Linda S, Arveiler, Dominique, Haessler, Jeffrey, Assimes, Themistocles L, Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O, Boomsma, Dorret I, Borecki, Ingrid B, Bornstein, Stefan R, Bovet, Pascal, Burnier, Michel, Hall, Per, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chen, Yii-Der Ida, Collins, Francis S, Cooper, Richard S, Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B, Haller, Toomas, Ferrieres, Jean, Ferrucci, Luigi, Freimer, Nelson B, Gieger, Christian, Groop, Leif C, Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Hingorani, Aroon, Hallmans, Goran, Hofman, Albert, Hovingh, G Kees, Hsiung, Chao Agnes, Humphries, Steve E, Hunt, Steven C, Hveem, Kristian, Iribarren, Carlos, Jarvelin, Marjo-Riitta, Jula, Antti, Hartman, Catharina A, Kähönen, Mika, Kaprio, Jaakko, Kesäniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S, Koudstaal, Peter J, Krauss, Ronald M, Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O, Hassinen, Maija, Laakso, Markku, Lakka, Timo A, Lind, Lars, Lindgren, Cecilia M, Martin, Nicholas G, März, Winfried, McCarthy, Mark I, McKenzie, Colin A, Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D, Munroe, Patricia B, Njølstad, Inger, Pedersen, Nancy L, Power, Chris, Pramstaller, Peter P, Price, Jackie F, Psaty, Bruce M, Quertermous, Thomas, Heard-Costa, Nancy L, Rauramaa, Rainer, Saleheen, Danish, Salomaa, Veikko, Sanghera, Dharambir K, Saramies, Jouko, Schwarz, Peter E H, Sheu, Wayne H-H, Shuldiner, Alan R, Siegbahn, Agneta, Spector, Tim D, Helmer, Quinta, Stefansson, Kari, Strachan, David P, Tayo, Bamidele O, Tremoli, Elena, Uusitupa, Matti, van Duijn, Cornelia M, Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J, Hengstenberg, Christian, Whitfield, John B, Wolffenbuttel, Bruce H R, Ordovas, Jose M, Boerwinkle, Eric, Palmer, Colin N A, Thorsteinsdottir, Unnur, Chasman, Daniel I, Rotter, Jerome I, Franks, Paul W, Ripatti, Samuli, Holmen, Oddgeir, Cupples, L Adrienne, Sandhu, Manjinder S, Rich, Stephen S, Boehnke, Michael, Deloukas, Panos, Kathiresan, Sekar, Mohlke, Karen L, Ingelsson, Erik, Abecasis, Gonçalo R, Abecasis, Gonçalo, Hottenga, Jouke-Jan, Caulfield, Mark, Chasman, Dan, Ehret, Georg, Johnson, Andrew, Johnson, Louise, Larson, Martin, Levy, Daniel, James, Alan L, Munroe, Patricia, Newton-Cheh, Christopher, O'Reilly, Paul, Palmas, Walter, Psaty, Bruce, Rice, Kenneth, Smith, Albert, Snider, Harold, Tobin, Martin, Van Duijn, Cornelia, Jeff, Janina M, Verwoert, Germaine, Rice, Kenneth M, Johnson, Andrew D, Smith, Albert V, Tobin, Martin D, Verwoert, Germaine C, Hwang, Shih-Jen, Pihur, Vasyl, O'Reilly, Paul F, Amin, Najaf, Teumer, Alexander, Glazer, Nicole L, Launer, Lenore, Jolley, Jennifer, Aulchenko, Yurii, Heath, Simon, Sõber, Siim, Parsa, Afshin, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Juliusdottir, Thorhildur, Peden, John F, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N, Fava, Cristiano, Kinnunen, Leena, Fox, Ervin R, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Koenig, Wolfgang, Whincup, Peter H, Liu, Yongmei, Shi, Gang, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Nguyen, Khanh-Dung Hoang, Lehtimäki, Terho, Matullo, Giuseppe, Koskenvuo, Markku, Gaunt, Tom R, Onland-Moret, N Charlotte, Cooper, Matthew N, Platou, Carl G P, Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Kratzer, Wolfgang, Braund, Peter S, Kuznetsova, Tatiana, Uiterwaal, Cuno S P M, Adeyemo, Adebowale, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D, Laitinen, Jaana, Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C, Steinle, Nanette I, Grobbee, Diederick E, Arking, Dan E, Kardia, Sharon L, Morrison, Alanna C, Lamina, Claudia, Najjar, Samer, Hadley, David, Brown, Morris J, Connell, John M, Hingorani, Aroon D, Day, Ian N M, Lawlor, Debbie A, Beilby, John P, Lawrence, Robert W, Leander, Karin, Clarke, Robert, Collins, Rory, Hopewell, Jemma C, Ongen, Halit, Dreisbach, Albert W, Li, Yali, Young, J. H., Bis, Joshua C, Viikari, Jorma, Lee, Nanette R, Chen, Ming-Huei, Olden, Matthias, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Lichtner, Peter, Frayling, Timothy M, Islam, Muhammad, Jafar, Tazeen H, Erdmann, Jeanette, Kulkarni, Smita R, Grässler, Jürgen, Howard, Philip, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Weder, Alan B, Lindström, Jaana, Sun, Yan V, Bergman, Richard N, Scott, Laura J, Stringham, Heather M, Peltonen, Leena, Vartiainen, Erkki, Brand, Stefan-Martin, Kutalik, Zoltán, Lo, Ken Sin, Staessen, Jan A, Wang, Thomas J, Burton, Paul R, Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K, Rudock, Megan E, Lobbens, Stéphane, Heckbert, Susan R, Smith, Nicholas L, Wiggins, Kerri L, Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairajan, Tripathy, Vikal, Lorbeer, Roberto, Langefeld, Carl D, Rosengren, Annika, Thelle, Dag S, Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, Salako, Tunde, Iwai, Naoharu, Lu, Yingchang, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, H-Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, James, Sehmi, Joban S, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Raffel, Leslie J, Yao, Jie, O'Donnell, Chris, Schwartz, Stephen M, Ikram, M Arfan, Longstreth, W. T., Mosley, Thomas H, Seshadri, Sudha, Mahajan, Anubha, Shrine, Nick R G, Wain, Louise V, Morken, Mario A, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A, Rasheed, Asif, Goel, Anuj, Watkins, Hugh, Bakker, Stephan J L, van Gilst, Wiek H, Janipalli, Charles S, Mani, K Radha, Yajnik, Chittaranjan S, McLachlan, Stela, Mattace-Raso, Francesco U S, Oostra, Ben A, Demirkan, Ayse, Lakatta, Edward G, Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J, Menni, Cristina, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Ong, Rick Twee-Hee, Dörr, Marcus, Kroemer, Heyo K, Völker, Uwe, Völzke, Henry, Galan, Pilar, Merger, Sigrun, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Zhai, Guangju, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Terzic, Janos, Kumar, M J Kranthi, Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E, Fowkes, F Gerald R, Charchar, Fadi J, Guo, Xiuqing, Milani, Lili, Rotimi, Charles, Bots, Michiel L, Brand, Eva, Samani, Nilesh J, Polasek, Ozren, Talmud, Philippa J, Nyberg, Fredrik, Laan, Maris, Moayyeri, Alireza, Palmer, Lyle J, van der Schouw, Yvonne T, Casas, Juan P, Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K, Wong, Tien Y, Tai, E Shyong, Monda, Keri L, Rao, Dabeeru C, Morris, Richard W, Dominiczak, Anna F, Marmot, Michael G, Miki, Tetsuro, Chandak, Giriraj R, Coresh, Josef, Navis, Gerjan, Han, Bok-Ghee, Zhu, Xiaofeng, Melander, Olle, Gyllensten, Ulf B, Mulas, Antonella, Wright, Alan F, Farrall, Martin, Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J G, Altshuler, David, Müller, Gabriele, Rettig, Rainer, Uda, Manuela, Witteman, Jacqueline C M, Vasan, Ramachandran S, Larson, Martin G, Järvelin, Marjo-Riitta, Musk, Arthur W, Caulfield, Mark J, Alizadeh, Behrooz Z, de Boer, Rudolf A, Mägi, Reedik, Boezen, H Marike, Bruinenberg, Marcel, Franke, Lude, Hillege, Hans L, van der Klauw, Melanie M, Ormel, Johan, Postma, Dirkje S, Rosmalen, Judith G M, Nöthen, Markus M, Slaets, Joris P, Stolk, Ronald P, Scott, Robert A, Lagou, Vasiliki, Welch, Ryan P, Wheeler, Eleanor, Rehnberg, Emil, Rasmussen-Torvik, Laura J, Yengo, Loïc, Lecoeur, Cecile, Pilz, Stefan, Johnson, Paul C D, Jukema, J Wouter, Verweij, Niek, Rayner, Nigel W, Sennblad, Bengt, Salo, Perttu, Timpson, Nicholas J, Evans, David M, St Pourcain, Beate, Andrews, Jeanette S, Renstrom, Frida, Hui, Jennie, Bielak, Lawrence F, Zhao, Wei, Horikoshi, Momoko, Navarro, Pau, Esko, Tönu, Raychaudhuri, Soumya, Chen, Han, Morris, Andrew P, Ried, Janina S, Robertson, Neil, Rybin, Denis, Liu, Ching-Ti, Willems, Sara M, Chines, Peter S, Kang, Hyun Min, Song, Kijoung, Ripke, Stephan, An, Ping, Franco-Cereceda, Anders, Marullo, Letizia, Jansen, Hanneke, Robertson, Neil R, Oldehinkel, Albertine J, Pankow, James S, North, Kari E, Forouhi, Nita G, Edkins, Sarah, Varga, Tibor V, Oksa, Heikki, Randall, Joshua C, Rose, Lynda M, Antonella, Mulas, Trompet, Stella, Ford, Ian, Kong, Augustine, Herder, Christian, Antti, Jula, Small, Kerrin, Miljkovic, Iva, Atalay, Mustafa, Kiess, Wieland, Smit, Johannes H, Campbell, Susan, Scholtens, Salome, Fowkes, Gerard R, Kovacs, Peter, Zemunik, Tatijana, Basart, Hanneke V, Rathmann, Wolfgang, Schumacher, Fredrick R, Maerz, Winfried, Peters, Annette, Province, Michael A, Hastie, Nicholas D, Scott, William R, Stumvoll, Michael, Waterworth, Dawn M, Watanabe, Richard M, de Geus, Eco J C, Seufferlein, Thomas, Penninx, Brenda W, Shi, Jianxin, Dedoussis, George V, Smith, Albert Vernon, Toenjes, Anke, Peyser, Patricia A, Körner, Antje, Smolonska, Joanna, Winkler, Thomas W, Stanton, Alice V, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Dupuis, Josée, Sattar, Naveed, Steinthorsdottir, Valgerdur, Cucca, Francesco, Balkau, Beverley, Froguel, Philippe, Bouatia-Naji, Nabila, Meigs, James B, Purcell, Shaun, Musunuru, Kiran, Ardissino, Diego, Mannucci, Pier M, Anand, Sonia, Engert, James C, Schunkert, Heribert, Sundström, Johan, Morgan, Thomas, Spertus, John A, Stoll, Monika, Girelli, Domenico, McKeown, Pascal P, Patterson, Chris C, Siscovick, David S, O'Donnell, Christopher J, Swertz, Morris A, Merlini, Pier Angelica, Berzuini, Carlo, Bernardinelli, Luisa, Peyvandi, Flora, Tubaro, Marco, Celli, Patrizia, Ferrario, Maurizio, Fetiveau, Raffaela, Marziliano, Nicola, Casari, Giorgio, Galli, Michele, Ribichini, Flavio, Rossi, Marco, Syvänen, Ann-Christine, Bernardi, Francesco, Zonzin, Pietro, Piazza, Alberto, Yee, Jean, Friedlander, Yechiel, Marrugat, Jaume, Tan, Sian-Tsung, Subirana, Isaac, Sala, Joan, Ramos, Rafael, Williams, Gordon, Nathan, David M, MacRae, Calum A, Havulinna, Aki S, Berglund, Goran, Asselta, Rosanna, Duga, Stefano, Berndt, Sonja I, Wood, Andrew R, Thorand, Barbara, Spreafico, Marta, Daly, Mark J, Nemesh, James, Korn, Joshua M, McCarroll, Steven A, Surti, Aarti, Gianniny, Lauren, Mirel, Daniel, Parkin, Melissa, Tyrer, Jonathan P, Burtt, Noel, Gabriel, Stacey B, Thompson, John R, Wright, Benjamin J, Balmforth, Anthony J, Ball, Stephen G, Hall, Alistair S, Schunkert, I Heribert, Uh, Hae-Won, Linsel-Nitschke, Patrick, Lieb, Wolfgang, Ziegler, Andreas, König, Inke R, Fischer, Marcus, Stark, Klaus, Grosshennig, Anika, Preuss, Michael, Vandenput, Liesbeth, Schreiber, Stefan, Ouwehand, Willem, Scholz, Michael, Cambien, Francois, Verhulst, Frank C, Goodall, Alison, Li, Mingyao, Chen, Zhen, Wilensky, Robert, Matthai, William, Qasim, Atif, Hakonarson, Hakon H, Devaney, Joe, Burnett, Mary-Susan, Vermeulen, Sita H, Pichard, Augusto D, Kent, Kenneth M, Satler, Lowell, Lindsay, Joseph M, Waksman, Ron, Knouff, Christopher W, Walker, Max C, Scheffold, Thomas, Berger, Klaus, Huge, Andreas, Martinelli, Nicola, Olivieri, Oliviero, Corrocher, Roberto, Vonk, Judith M, Hólm, Hilma, Workalemahu, Tsegaselassie, Warren, Helen R, Xie, Changchun, Siscovick, David, Waterworth, Dawn, Ahmadi, Kourosh R, Ainali, Chrysanthi, Barrett, Amy, Bataille, Veronique, Weedon, Michael N, Bell, Jordana T, Buil, Alfonso, Dermitzakis, Emmanouil T, Dimas, Antigone S, Durbin, Richard, Glass, Daniel, Grundberg, Elin, Hassanali, Neelam, Hedman, Åsa K, Wilkens, Lynne R, Ingle, Catherine, Keildson, Sarah, Knowles, David, Krestyaninova, Maria, Lowe, Christopher E, Meduri, Eshwar, di Meglio, Paola, Min, Josine L, Willenborg, Christina, Montgomery, Stephen B, Nestle, Frank O, Nica, Alexandra C, Nisbet, James, O'Rahilly, Stephen, Parts, Leopold, Potter, Simon, Sekowska, Magdalena, Shin, So-Youn, Small, Kerrin S, Surdulescu, Gabriela, Travers, Mary E, Tsaprouni, Loukia, Tsoka, Sophia, Wilk, Alicja, Yang, Tsun-Po, Zondervan, Krina T, Matise, Tara, Wojczynski, Mary K, Buyske, Steve, Higashio, Julia, Williams, Rasheeda, Nato, Andrew, Ambite, Jose Luis, Deelman, Ewa, Manolio, Teri, Hindorff, Lucia, Heiss, Gerardo, Taylor, Kira, Franceschini, Nora, Avery, Christy, Graff, Misa, Lin, Danyu, Quibrera, Miguel, Cochran, Barbara, Kao, Linda, Umans, Jason, Cole, Shelley, MacCluer, Jean, Person, Sharina, Pankow, James, Gross, Myron, Fornage, Myriam, Durda, Peter, Jenny, Nancy, Patsy, Bruce, Arnold, Alice, Zhang, Qunyuan, Buzkova, Petra, Crawford, Dana, Haines, Jonathan, Murdock, Deborah, Glenn, Kim, Brown-Gentry, Kristin, Thornton-Wells, Tricia, Dumitrescu, Logan, Jeff, Janina, Bush, William S, Faul, Jessica D, Study, LifeLines Cohort, Mitchell, Sabrina L, Goodloe, Robert, Wilson, Sarah, Boston, Jonathan, Malinowski, Jennifer, Restrepo, Nicole, Oetjens, Matthew, Fowke, Jay, Zheng, Wei, Spencer, Kylee, Brennan, Eoin P, Ritchie, Marylyn, Pendergrass, Sarah, Le Marchand, Loïc, Wilkens, Lynne, Park, Lani, Tiirikainen, Maarit, Kolonel, Laurence, Lim, Unhee, Cheng, Iona, Wang, Hansong, Choi, Murim, Shohet, Ralph, Haiman, Christopher, Stram, Daniel, Henderson, Brian, Monroe, Kristine, Schumacher, Fredrick, Kooperberg, Charles, Peters, Ulrike, Anderson, Garnet, Carlson, Chris, Dastani, Zari, Prentice, Ross, LaCroix, Andrea, Wu, Chunyuan, Carty, Cara, Gong, Jian, Rosse, Stephanie, Young, Alicia, Haessler, Jeff, Kocarnik, Jonathan, Lin, Yi, Drong, Alexander W, Jackson, Rebecca, Duggan, David, Kuller, Lew, Stolk, Lisette, Perry, John R B, He, Chunyan, Sulem, Patrick, Barbalic, Maja, Eriksson, Per, Broer, Linda, Byrne, Enda M, Ernst, Florian, Gudbjartsson, Daniel F, Kraft, Peter, McArdle, Patick F, Porcu, Eleonora, van Wingerden, Sophie, Zhuang, Wei V, Albrecht, Eva, Lauc, Lovorka Barac, Gådin, Jesper R, Boban, Mladen, Broekmans, Frank J, Burri, Andrea, Chanock, Stephen J, Chen, Constance, Cornelis, Marilyn C, Corre, Tanguy, Gharavi, Ali G, Coviello, Andrea D, d'Adamo, Pio, Davies, Gail, Deary, Ian J, Dedoussis, George V Z, Deloukas, Panagiotis, Ebrahim, Shah, Eiriksdottir, Gudny, Goddard, Michael E, Eriksson, Johan G, Fauser, Bart C J M, Ferreli, Liana, Folsom, Aaron R, Gasparini, Paolo, Smith, Jennifer A, Handsaker, Robert E, Glazer, Nicole, Hankinson, Susan E, Hass, Merli, Heath, Andrew C, Huang, Jinyan, Janssens, A Cecile J W, Karasik, David, Kardia, Sharon L R, Keyzer, Jules, Kiel, Douglas P, Kolcic, Ivana, Lahti, Jari, Lai, Sandra, Karpe, Fredrik, Laisk, Triin, Laven, Joop S E, Liu, Jianjun, Lopez, Lorna M, Louwers, Yvonne V, Marongiu, Mara, Klaric, Irena Martinovic, Masciullo, Corrado, McKnight, Barbara, Medland, Sarah E, Melzer, David, Newman, Anne B, Nyholt, Dale R, Paré, Guillaume, Peeters, Petra H M, Pistis, Giorgio, Plump, Andrew S, Pop, Victor J M, Räikkönen, Katri, Kiryluk, Krzysztof, Sala, Cinzia, Salumets, Andres, Kubo, Michiaki, Stacey, Simon N, Starr, John M, Stathopoulou, Maria G, Styrkarsdottir, Unnur, Tenesa, Albert, Toniolo, Daniela, Tryggvadottir, Laufey, Tsui, Kim, Ulivi, Sheila, van Dam, Rob M, van Gils, Carla H, van Nierop, Peter, Vink, Jacqueline M, Visscher, Peter M, Voorhuis, Marlies, Liang, Liming, Waeber, Gérard, Wallaschofski, Henri, Wichmann, H Erich, Widen, Elisabeth, Wijnands-van Gent, Colette J M, Yerges-Armstrong, Laura M, Lifton, Richard P, Zgaga, Lina, Zillikens, M Carola, Zygmunt, Marek, Arnold, Alice M, Buring, Julie E, Crisponi, Laura, Demerath, Ellen W, Ma, Baoshan, Hu, Frank B, Hunter, David J, Launer, Lenore J, Montgomery, Grant W, Schlessinger, David, Streeten, Elizabeth A, Uitterlinden, André G, Murray, Anna, Murabito, Joanne M, McKnight, Amy J, Visser, Jenny A, Lunetta, Kathryn L, Elks, Cathy E, Cousminer, Diana L, Feenstra, Bjarke, Koller, Daniel L, Lin, Peng, Moffatt, Miriam F, McArdle, Patrick F, van Wingerden, Sophie W, Smith, Erin N, Ulivi, Shelia, Warrington, Nicole M, Alavere, Helen, Barroso, Ines, Berenson, Gerald S, Blackburn, Hannah, Busonero, Fabio, Chen, Wei, Nicholson, George, Couper, David, Döring, Angela, Easton, Douglas F, Eriksson, Johan, Foroud, Tatiana, Okada, Yukinori, Hernandez, Dena G, Kilpeläinen, Tuomas O, Li, Shengxu, Dorajoo, Rajkumar, Melbye, Mads, Murray, Jeffrey C, Murray, Sarah S, Nelis, Mari, Reinmaa, Eva, Ness, Andrew R, Northstone, Kate, Peacock, Munro, Salem, Rany M, Pennell, Craig E, Pharoah, Paul, Rafnar, Thorunn, Rice, John P, Ring, Susan M, Sandholm, Niina, Schork, Nicholas J, Segrè, Ayellet V, Sovio, Ulla, Srinivasan, Sathanur R, Tammesoo, 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EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Eriksson, J., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Peacock, M., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., van Meurs JB., Weedon, MN., Wichmann, H., Young, L., Bierut, LJ., Boyd, HA., Econs, MJ., Van T'Hooft, Ferdinand M., Njølstad, Inger, Abecasis, Gonçalo R., Barroso, Inɥ, The MIGEN Consortium, Investigator, Casari, GIORGIO NEVIO, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Landsteiner Laboratory, Clinical Haematology, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life 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Mangino, M, Leach, I, Medina-Gomez, C, Medland, S, Nalls, M, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Shungin, D, Stancakova, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet-Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Isaacs, A, Albrecht, E, Arnlov, J, Arscott, G, Attwood, A, Bandinelli, S, Barrett, A, Bas, I, Bellis, C, Bennett, A, Berne, C, Blagieva, R, Bluher, M, Bohringer, S, Bonnycastle, L, Bottcher, Y, Boyd, H, Bruinenberg, M, Caspersen, I, Chen, Y, Clarke, R, Daw, E, de Craen, A, Delgado, G, Dimitriou, M, Doney, A, Eklund, N, Estrada, K, Eury, E, Folkersen, L, Fraser, R, Garcia, M, Geller, F, Giedraitis, V, Gigante, B, Go, A, Golay, A, Goodall, A, Gordon, S, Gorski, M, Grabe, H, Grallert, H, Grammer, T, Grassler, J, Gronberg, H, Groves, C, Gusto, G, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heard-Costa, N, Helmer, Q, Hengstenberg, C, Holmen, O, Hottenga, J, James, A, Jeff, J, Johansson, A, Jolley, J, Juliusdottir, T, Kinnunen, L, Koenig, W, Koskenvuo, M, Kratzer, W, Laitinen, J, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindstrom, J, Lo, K, Lobbens, S, Lorbeer, R, Lu, Y, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Mclachlan, S, Menni, C, Merger, S, Mihailov, E, Milani, L, Moayyeri, A, Monda, K, Morken, M, Mulas, A, Muller, G, Muller-Nurasyid, M, Musk, A, Nagaraja, R, Nothen, M, Nolte, I, Pilz, S, Rayner, N, Renstrom, F, Rettig, R, Ried, J, Ripke, S, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Scott, W, Seufferlein, T, Shi, J, Smith, A, Smolonska, J, Stanton, A, Steinthorsdottir, V, Stirrups, K, Stringham, H, Sundstrom, J, Swertz, M, Swift, A, Syvanen, A, Tan, S, Tayo, B, Thorand, B, Thorleifsson, G, Tyrer, J, Uh, H, Vandenput, L, Verhulst, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Warren, H, Waterworth, D, Weedon, M, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, 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S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Makinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkila, O, Hietala, K, Kyto, J, Lahermo, P, Lehto, M, Osterholm, A, Parkkonen, M, Pitkaniemi, J, Rosengard-Barlund, M, Saraheimo, M, Sarti, C, Soderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Waden, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc-Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Mollsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Freitag, D, Gurdasani, D, Heikkila, K, Johnson, T, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Teslovich, T, Van den Herik, E, Volcik, K, Wu, Y, Asiki, G, Been, L, Burnett, M, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Khaw, K, Kim, E, Komulainen, P, Lin, S, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Young, E, Bennett, F, Boomsma, D, Burnier, M, Feranil, A, Freimer, N, Hsiung, C, Kesaniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Meneton, P, Moilanen, L, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton-Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sober, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjogren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland-Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Brown, M, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Staessen, J, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Smith, G, Raffel, L, Yao, J, Schwartz, S, Ikram, M, W, L, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace-Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Wurtz, P, Ong, R, Dorr, M, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Guo, X, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, Palmer, L, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Alizadeh, B, de Boer, R, Boezen, H, Hillege, H, van der Klauw, M, Ormel, J, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Rasmussen-Torvik, L, Lecoeur, C, Johnson, P, Sennblad, B, Salo, P, Timpson, N, Evans, D, St Pourcain, B, Bielak, L, Horikoshi, M, Navarro, P, Raychaudhuri, S, Chen, H, Rybin, D, Willems, S, Song, K, An, P, Marullo, L, Jansen, H, Pankow, J, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Small, K, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Penninx, B, Toenjes, A, Peyser, P, Korner, A, Dupuis, J, Cucca, F, Balkau, B, Bouatia-Naji, N, Purcell, S, Musunuru, K, Ardissino, D, Mannucci, P, Anand, S, Engert, J, Morgan, T, Spertus, J, Stoll, M, Girelli, D, Mckeown, P, Patterson, C, Merlini, P, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Subirana, I, Sala, J, Ramos, R, Williams, G, Nathan, D, Macrae, C, Berglund, G, Asselta, R, Duga, S, Spreafico, M, Daly, M, Nemesh, J, Korn, J, Surti, A, Gianniny, L, Parkin, M, Burtt, N, Gabriel, S, Wright, B, Ball, S, Schunkert, I, Linsel-Nitschke, P, Lieb, W, Fischer, M, Grosshennig, A, Preuss, M, Scholz, M, Chen, Z, Wilensky, R, Matthai, W, Qasim, A, Hakonarson, H, Devaney, J, Pichard, A, Kent, K, Satler, L, Lindsay, J, Waksman, R, Knouff, C, Scheffold, T, Berger, K, Huge, A, Martinelli, N, Olivieri, O, Corrocher, R, Xie, C, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, Di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Yang, T, Higashio, J, Williams, R, Nato, A, Ambite, J, Deelman, E, Manolio, T, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown-Gentry, K, Thornton-Wells, T, Dumitrescu, L, Bush, W, Mitchell, S, Goodloe, R, Wilson, S, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Spencer, K, Pendergrass, S, Le Marchand, L, Park, L, Tiirikainen, M, Kolonel, L, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Anderson, G, Carlson, C, Prentice, R, Lacroix, A, Wu, C, Carty, C, Rosse, S, Young, A, Kocarnik, J, Lin, Y, Jackson, R, Duggan, D, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hankinson, S, Hass, M, Janssens, A, Karasik, D, Keyzer, J, Kiel, D, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Melzer, D, Newman, A, Pare, G, Peeters, P, Pop, V, Raikkonen, K, Salumets, A, Stacey, S, Starr, J, Stathopoulou, M, Styrkarsdottir, U, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Widen, E, Wijnands-Van Gent, C, Yerges-Armstrong, L, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Streeten, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Koller, D, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Couper, D, Easton, D, Foroud, T, Kilpelainen, T, Li, S, Murray, S, Ness, A, Northstone, K, Peacock, M, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segre, A, Sovio, U, Srinivasan, S, Tammesoo, M, van Meurs, J, Young, L, Bierut, L, Econs, M, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium, Berndt, Sonja I, Justice, Anne E, Hyppönen, Elina Tuulikki, Epidemiology and Data Science, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes

Subjects
Male, LOCI, Genome-wide association study, Continental Population Groups/genetics, VARIANTS, Body Mass Index, Insulin Secretion, Insulin, Age Factor, Adiposity, ddc:616, Adipogenesis, Genetic Predisposition to Disease/genetics, Synapse, 3. Good health, Continental Population Group, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], GENOME-WIDE ASSOCIATIONPROVIDES INSIGHTSGLYCEMIC TRAITSLOCIMETAANALYSISVARIANTSINDIVIDUALSHIPPOCAMPALARCHITECTURETOPIRAMATE, ddc:500, Adipogenesis/genetics, Single Nucleotide/genetics, Age Factors, Continental Population Groups, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Glutamic Acid, Humans, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses, Genome-Wide Association Study, Multidisciplinary, genetics [Adiposity], Human, Socio-culturale, genetics [Energy Metabolism], ta3111, genetic, body mass index, obesity, SDG 3 - Good Health and Well-being, GLYCEMIC TRAITS, genetics [Continental Population Groups], Genetic variability, Polymorphism, GENOME-WIDE ASSOCIATION, genetics [Adipogenesis], METAANALYSIS, Genetic association, Adipogenesi, genetics [Quantitative Trait Loci], ta1184, metabolism [Glutamic Acid], ta1182, PATHWAYS, metabolism [Synapses], ta3121, medicine.disease, metabolism [Insulin], Adiposity/genetics, Clinical Medicine, Quantitative Trait Loci/genetics, Body mass index, HUMAN HEIGHT, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Synapses/metabolism, Medizin, Obesity/genetics, Bioinformatics, genetic basis, Obesity/metabolism, genetics [Obesity], body mass index (BMI), genetics [Genetic Predisposition to Disease], ethnology [Europe], 2. Zero hunger, Genetics, ARCHITECTURE, Genetics of obesity, Medicine (all), Single Nucleotide, Polymorphism, Single Nucleotide/genetics, Insulin/metabolism/secretion, Glutamic Acid/metabolism, genetics [Polymorphism, Single Nucleotide], EXPRESSION, Insulin/metabolism, PROVIDES INSIGHTS, genetics [Racial Groups], Biology, Obesity/genetics/metabolism, Europe/ethnology, metabolism [Obesity], Mendelian randomization, medicine, Energy Metabolism/genetics, body mass, genetic analysis, obesity, Klinisk medicin
Abstract

Item does not contain fulltext Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Published
2015

29. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, Dmitry, Winkler, Thomas W, Workalemahu, Tsegaselassie, Hartman, Catharina A, Duncan, Emma L, Ntzani, Evangelia E, Oei, Ling, Albagha, Omar M E, Amin, Najaf, Kemp, John P, Koller, Daniel L, Li, Guo, Liu, Ching-Ti, Minster, Ryan L, Hassinen, Maija, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Yerges-Armstrong, Laura M, Zheng, Hou-Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M, Kaptoge, Stephen K, Hayward, Caroline, Leo, Paul J, Thorleifsson, Gudmar, Wilson, Scott G, Wilson, James F, Aalto, Ville, Alen, Markku, Aragaki, Aaron K, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Heikkilä, Kauko, Duggan, David J, Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J, Husted, Lise Bjerre, Jameson, Karen A, Khusainova, Rita, Kim, Ghi Su, Herzig, Karl-Heinz, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z, Lee, Seung Hun, Leung, Ping C, Lewis, Joshua R, Masi, Laura, Mencej-Bedrac, Simona, Helmer, Quinta, Nguyen, Tuan V, Nogues, Xavier, Patel, Millan S, Prezelj, Janez, Rose, Lynda M, Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V, Svensson, Olle, Trompet, Stella, Hillege, Hans L, Trummer, Olivia, van Schoor, Natasja M, Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M, Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Holmen, Oddgeir, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Hunt, Steven C, Langdahl, Bente Lomholt, Leslie, William D, Lips, Paul, Ljunggren, Östen, Lorenc, Roman S, Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M, Pettersson-Kymmer, Ulrika, Isaacs, Aaron, Reid, David M, Riancho, José A, Ridker, Paul M, Rousseau, François, Slagboom, P Eline, Tang, Nelson L S, Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T, Wu, Joseph M W, 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Edgar E, Bataille, Veronique, Bell, Jordana T, Buil, Alfonso, Dermitzakis, Emmanouil T, Dimas, Antigone S, Durbin, Richard, Glass, Daniel, Hassanali, Neelam, Westra, Harm-Jan, Ingle, Catherine, Knowles, David, Krestyaninova, Maria, Lowe, Christopher E, Meduri, Eshwar, di Meglio, Paola, Montgomery, Stephen B, Nestle, Frank O, Nica, Alexandra C, Nisbet, James, O'Rahilly, Stephen, Parts, Leopold, Potter, Simon, Sekowska, Magdalena, Shin, So-Youn, Consortium, ADIPOGen, Small, Kerrin S, Surdulescu, Gabriela, Travers, Mary E, Tsaprouni, Loukia, Tsoka, Sophia, Wilk, Alicja, Yang, Tsun-Po, Consortium, CARDIOGRAMplusC4D, Matise, Tara, Buyske, Steve, Higashio, Julia, Williams, Rasheeda, Nato, Andrew, Ambite, Jose Luis, Deelman, Ewa, Manolio, Teri, Hindorff, Lucia, Consortium, CKDGen, Heiss, Gerardo, Taylor, Kira, Franceschini, Nora, Avery, Christy, Graff, Misa, Lin, Danyu, Quibrera, Miguel, Cochran, Barbara, Kao, Linda, Umans, Jason, Consortium, GEFOS, Cole, Shelley, MacCluer, Jean, Person, 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Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Department of Clinical Sciences, Lund University [Lund], Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Umeå University, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, Limnology, Ecology, Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Institute of Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetic Epidemiology Unit, 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Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of California [Irvine] (UCI), German Research Center for Environmental Health, University of Bonn, Czech Academy of Sciences [Prague] (ASCR), Yale University School of Medicine, University of Oxford [Oxford], German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Laval University, Laval University [Québec], Turku University Hospital, Lausanne university hospital, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Helmholtz-Zentrum München (HZM), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Medical Informatics, Obstetrics & Gynecology, Lund University [Lund]-Lund University Diabetes Centre, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institute of Medicine-University of Gothenburg (GU), Signalisation et Transports Ioniques Membranaires ( STIM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Technical University of Denmark [Lyngby] ( DTU ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Department of Medical Epidemiology and Biostatistics ( MEB ), University of Lausanne, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC, Space Sciences Laboratory [Berkeley] ( SSL ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of Leipzig, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Epidemiology [Neuherberg] ( EPI ), University of California [Irvine] ( UCI ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Geneva University Hospital ( HUG ), Bonn Universität [Bonn], Indian Institute of Technology Kanpur ( IIT Kanpur ), The University of North Carolina at Chapel Hill, Université de Bonn, Wellcome Trust Sanger Institute, Harvard University School of Public Health, Czech Academy of Sciences [Prague] ( ASCR ), deCODE genetics, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Yale School of Medicine, National Heart and Lung Institute ( NHLI ), 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, Droit et Santé, University Medical Center Groningen, University of Cambridge [UK] ( CAM ), Wellcome Trust Centre for Human Genetics, University of Pisa [Pisa], University of Cambridge [UK] ( CAM ) -Institute of Metabolic Science, German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), University of Otago, University of Greifswald, University College of London [London] ( UCL ), National Institute for Health and Welfare, Queen's University [Belfast] ( QUB ), University of Hawaii at Manoa ( UHM ), University of Gothenburg ( GU ) -Institute of Medicine, Recherches en Psychopathologie, nouveaux symptômes et lien social ( EA 4050 ), Université de Poitiers-Université de Brest ( UBO ) -Université Catholique de l'Ouest-Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Finland Institute for Molecular Medicine ( FIMM ), Georgia Prevention Institute, Netherlands Consortium for Healthy Aging, Helmholtz-Zentrum München ( HZM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Massachusetts General Hospital, Children's Hospital, Boston, Broad Institute, Cambridge, MA, The University of North Carolina at Chapel Hill-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Shungin D, Winkler TW, Adipogen, Consortium, Cardiogramplusc4d, Consortium, Ckdgen, Consortium, Gefos, Consortium, Genie, Consortium, Glgc, Icbp, International, Endogene Consortium, Lifelines, Cohort Study, Magic, Investigator, Muther, Consortium, Consortium, Page, ReproGen Consortium, Amouyel P, D'Adamo, ADAMO PIO, Gasparini, Paolo, Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Hypponen, Elina, Mohlke, Karen L, ADIPOGEN Consortium, Int Endogene Consortium, Lee Kong Chian School of Medicine (LKCMedicine), Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, Pirastu, M, Jukema, J, Probst Hensch, N, Toniolo, D, Coresh, J, Schmidt, R, Kardia, S, Curhan, G, Gyllensten, U, Franke, A, Rettig, R, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, van der Harst, P, Arking, D, Franceschini, N, Hernandez, D, Townsend, R, Lumley, T, Kestenbaum, B, Haritunians, T, Waeber, G, Lu, X, Leak, T, Aasarød, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Beckmann, J, Dreisbach, A, Styrkarsdottir, U, Evangelou, E, Hsu, Y, Duncan, E, Ntzani, E, Oei, L, Albagha, O, Kemp, J, Koller, D, Minster, R, Vandenput, L, Willner, D, Xiao, S, Yerges Armstrong, L, Zheng, H, Alonso, N, Kammerer, C, Kaptoge, S, Leo, P, Wilson, S, Aalto, V, Alen, M, Aragaki, A, Center, J, Dailiana, Z, Duggan, D, Garcia Giralt, N, Giroux, S, Hocking, L, Husted, L, Jameson, K, Khusainova, R, Kim, G, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, A, Lee, S, Leung, P, Lewis, J, Masi, L, Mencej Bedrac, S, Nguyen, T, Nogues, X, Patel, M, Prezelj, J, Scollen, S, Siggeirsdottir, K, Svensson, O, Trummer, O, van Schoor, N, Woo, J, Zhu, K, Balcells, S, Brandi, M, Cheng, S, Christiansen, C, Cooper, C, Frost, M, Goltzman, D, González Macías, J, Karlsson, M, Khusnutdinova, E, Koh, J, Kollia, P, Langdahl, B, Leslie, W, Lips, P, Ljunggren, Ö, Lorenc, R, Marc, J, Mellström, D, Obermayer Pietsch, B, Olmos, J, Pettersson Kymmer, U, Reid, D, Riancho, J, Rousseau, F, Tang, N, Urreizti, R, Van Hul, W, Zarrabeitia, M, Castano Betancourt, M, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina Gómez, C, Palsson, S, Reppe, S, Sigurdsson, G, van Meurs, J, Verlaan, D, Williams, F, Zhou, Y, Gautvik, K, Raychaudhuri, S, Cauley, J, Clark, G, Cummings, S, Danoy, P, Dennison, E, Eastell, R, Eisman, J, Jackson, R, Jones, G, Khaw, K, Mccloskey, E, Nandakumar, K, Peacock, M, Pols, H, Prince, R, Reid, I, Robbins, J, Sambrook, P, Sham, P, Tylavsky, F, Econs, M, Kung, A, Reeve, J, Streeten, E, Karasik, D, Ralston, S, Ioannidis, J, Kiel, D, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Mäkinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkilä, O, Hietala, K, Kytö, J, Lahermo, P, Lehto, M, Österholm, A, Parkkonen, M, Pitkäniemi, J, Rosengård Bärlund, M, Saraheimo, M, Sarti, C, Söderlund, J, Soro Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Wadén, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Tregouet, D, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Möllsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Fraser, R, Freitag, D, Gurdasani, D, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Van den Herik, E, Volcik, K, Asiki, G, Been, L, Bolton, J, Bonnycastle, L, Burnett, M, Cesana, G, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Kastelein, J, Kim, E, Komulainen, P, Lin, S, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Stančáková, A, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Willemsen, G, Young, E, Bennett, F, Boomsma, D, Bovet, P, Chen, Y, Feranil, A, Freimer, N, Hsiung, C, Järvelin, M, Kesäniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Martin, N, Meneton, P, Moilanen, L, Njølstad, I, Price, J, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sõber, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjögren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Grässler, J, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Stanèáková, A, Raffel, L, Yao, J, Schwartz, S, Ikram, M, Longstreth W., J, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Morken, M, Laitinen, J, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Würtz, P, Ong, R, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Dominiczak, A, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Anderson, C, Gordon, S, Guo, Q, Henders, A, Lambert, A, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Alizadeh, B, de Boer, R, Boezen, H, van der Klauw, M, Ormel, J, Postma, D, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Lecoeur, C, Johnson, P, Hottenga, J, Salo, P, Bielak, L, Zhao, W, Horikoshi, M, Navarro, P, Chen, H, Rybin, D, Song, K, An, P, Marullo, L, Jansen, H, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Toenjes, A, Peyser, P, Körner, A, Cucca, F, Balkau, B, Bouatia Naji, N, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Hedman, Å, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Higashio, J, Williams, R, Nato, A, Ambite, J, Manolio, T, Hindorff, L, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown Gentry, K, Thornton Wells, T, Dumitrescu, L, Jeff, J, Bush, W, Mitchell, S, Goodloe, R, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Zheng, W, Spencer, K, Pendergrass, S, Wilkens, L, Park, L, Tiirikainen, M, Kolonel, L, Lim, U, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Schumacher, F, Anderson, G, Carlson, C, Prentice, R, Wu, C, Carty, C, Gong, J, Rosse, S, Young, A, Haessler, J, Kocarnik, J, Lin, Y, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chanock, S, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hall, P, Hankinson, S, Hass, M, Heath, A, Janssens, A, Keyzer, J, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Medland, S, Melzer, D, Newman, A, Paré, G, Peeters, P, Pop, V, Räikkönen, K, Salumets, A, Smith, J, Stacey, S, Starr, J, Stathopoulou, M, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Wallaschofski, H, Widen, E, Wijnands van Gent, C, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Feenstra, B, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Easton, D, Foroud, T, Geller, F, Kilpeläinen, T, Li, S, Melbye, M, Murray, J, Murray, S, Ness, A, Northstone, K, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segrè, A, Sovio, U, Srinivasan, S, Tammesoo, M, Tyrer, J, Weedon, M, Young, L, Bierut, L, Boyd, H, Psychiatry, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes

Subjects
Adipose Tissue/metabolism, Male, genetic association, subcutaneous fat, Transcription, Genetic, Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Mass Index, Continental Population Groups, Epigenesis, Genetic, Europe, Female, Genome, Human, Humans, Insulin, Insulin Resistance, Models, Biological, Neovascularization, Physiologic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics, Waist-Hip Ratio, Body Fat Distribution, Genome-Wide Association Study, Multidisciplinary, Insulin Resistance/genetics, Genome-wide association study, Continental Population Groups/genetics, genetic analysis, heritability, gene cluster, Science::Biological sciences::Human anatomy and physiology [DRNTU], 0302 clinical medicine, high density lipoprotein cholesterol, Models, genetics [Insulin Resistance], histone modification, Age Factor, insulin receptor, 0303 health sciences, Adipocyte, Human/genetics, CARDIOGRAMplusC4D Consortium, ADIPOGENIC DIFFERENTIATION, genetic correlation, body fat, Continental Population Group, priority journal, 5 trisphosphate 3 phosphatase, GEFOS Consortium, meta analysis (topic), Science & Technology - Other Topics, ddc:500, transcription regulation, Adipogenesis/genetics, Single Nucleotide/genetics, Human, medicine.medical_specialty, Waist, phosphatidylinositol 3, European, ta3111, genetic regulation, Article, developmental biology, 03 medical and health sciences, MAGIC Investigators, transcription initiation site, SDG 3 - Good Health and Well-being, Genetic, genomics, GLYCEMIC TRAITS, genetics [Continental Population Groups], Polymorphism, GENOME-WIDE ASSOCIATION, Physiologic, genetics [Adipogenesis], Adipocytes/metabolism, Europe/ethnology, Genome, Human/genetics, Insulin/metabolism, Neovascularization, Physiologic/genetics, Obesity/genetics, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Transcription, Genetic/genetics, Genetic/genetics, Adipogenesi, Science & Technology, adiponectin, [ SDV ] Life Sciences [q-bio], vasculotropin, genetics [Quantitative Trait Loci], ta1184, Racial Groups, ta1182, gene mapping, ta3121, triacylglycerol blood level, medicine.disease, Biological, major clinical study, amino acid sequence, metabolism [Insulin], Endocrinology, metabolism [Adipocytes], genetic loci, insulin, body fat, GLGC, International Endogene Consortium, metabolism [Adipose Tissue], Body mass index, HUMAN HEIGHT, Epigenesis, LifeLines Cohort Study, ReproGen Consortium, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, tissue level, Physiologic/genetics, [SDV]Life Sciences [q-bio], Medizin, Adipose tissue, low density lipoprotein cholesterol, PAGE Consortium, COMMON SNPS, angiogenesis, Waist–hip ratio, genetics [Obesity], MESH: Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, single nucleotide polymorphism, fat, genetic variability, molecular biology, body mass index (BMI), ethnology [Europe], peroxisome proliferator activated receptor, 2. Zero hunger, Genetics, Genome, Single Nucleotide, waist circumference, insulin, phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase, triacylglycerol, vasculotropin, developmental biology, gene expression, genome, numerical model, adipocyte, adipose tissue, body fat distribution, body mass, female, gene locus, gene structure, hip circumference, human, insulin resistance, lipoprotein blood level, male, obesity, protein protein interaction, sex difference, waist hip ratio, Multidisciplinary Sciences, genetics [Transcription, Genetic], genetics [Polymorphism, Single Nucleotide], ADIPOGen Consortium, genetics [Neovascularization, Physiologic], Transcription, SUSCEPTIBILITY LOCI, General Science & Technology, ICBP, 030209 endocrinology & metabolism, Biology, adipocyte, MESH : Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, MESENCHYMAL STEM-CELLS, GENIE Consortium, SEXUAL-DIMORPHISM, Insulin resistance, Internal medicine, medicine, genetics [Genome, Human], ABDOMINAL ADIPOSITY, Neovascularization, 030304 developmental biology, FALSE DISCOVERY, CKDGen Consortium, Sex Characteristic, MuTHER Consortium, numerical model
Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P

Published
2015

30. Blood lead levels in primary school children in Trinidad and Tobago

Author

Jay Manohar, Avril Siung-Chang, Rohit Doon, Ivan Chang-Yen, Michele A. Monteil, and Wayne Simon Rajkumar

Subjects
Male, medicine.medical_specialty, Environmental Engineering, education, Risk Assessment, Biological fluid, Environmental protection, Environmental health, Epidemiology, Humans, Environmental Chemistry, Medicine, Child, Waste Management and Disposal, West indies, medicine.diagnostic_test, business.industry, Public health, Baseline survey, Pollution, Trinidad and Tobago, Lead, El Niño, Child, Preschool, Environmental Pollutants, Female, Blood lead level, business, Risk assessment, Environmental Monitoring
Abstract

This study is the first national baseline survey of blood lead levels (BLLs) conducted on primary school children (ages 5-7 years) in Trinidad and Tobago. A total of 1,761 students from 61 schools participated in the study over a 3-month period. Measurements of capillary BLLs were assessed as well as responses to a risk assessment questionnaire. BLLs ranged from1 microg/dL to 28.6 microg/dL with a geometric mean of 2.8 microg/dL, which compared favourably with results from the U.S. 1991-94 National Health and Nutrition Examination Survey. Fifteen (0.9%) children had a BLLor=10 microg/dL (10.8-28.6 microg/dL) of which three (0.2%) met the U.S. criteria for lead poisoning (BLLor=20 microg/dL). Further environmental investigations are required to identify source(s) of lead exposure in cases with high BLL.

Published
2006

31. Granger causality-based synaptic weights estimation for analyzing neuronal networks

Author

Chien-Chang Yen, Pei-Chiang Shao, Meng-Li Tsai, Wei Chang Shann, Chen-Tung Yen, and Jian-Jia Huang

Subjects
Cognitive Neuroscience, Spike train, Models, Neurological, Action Potentials, Linear prediction, Inhibitory postsynaptic potential, Gyrus Cinguli, Causality (physics), Cellular and Molecular Neuroscience, Granger causality, Statistics, Humans, Computer Simulation, Mathematics, Artificial neural network, Linear model, Sensory Systems, Corpus Striatum, Electrophysiological Phenomena, Causality, Nonlinear Dynamics, Synapses, Excitatory postsynaptic potential, Linear Models, Neural Networks, Computer, Neuroscience, Algorithms
Abstract

Granger causality (GC) analysis has emerged as a powerful analytical method for estimating the causal relationship among various types of neural activity data. However, two problems remain not very clear and further researches are needed: (1) The GC measure is designed to be nonnegative in its original form, lacking of the trait for differentiating the effects of excitations and inhibitions between neurons. (2) How is the estimated causality related to the underlying synaptic weights? Based on the GC, we propose a computational algorithm under a best linear predictor assumption for analyzing neuronal networks by estimating the synaptic weights among them. Under this assumption, the GC analysis can be extended to measure both excitatory and inhibitory effects between neurons. The method was examined by three sorts of simulated networks: those with linear, almost linear, and nonlinear network structures. The method was also illustrated to analyze real spike train data from the anterior cingulate cortex (ACC) and the striatum (STR). The results showed, under the quinpirole administration, the significant existence of excitatory effects inside the ACC, excitatory effects from the ACC to the STR, and inhibitory effects inside the STR.

Published
2014

32. The connexin 30.3 of zebrafish homologue of human connexin 26 may play similar role in the inner ear

Author

Ju Chang-Chien, Shaun-Yow Li, Jiann-Jou Yang, Kuo-Hsuan Chien, Yung-Chang Yen, and Tsai-Ching Hsu

Subjects
Cytoplasm, animal structures, Time Factors, Genotype, Connexin, In situ hybridization, Biology, Transfection, Connexins, Morpholinos, otorhinolaryngologic diseases, medicine, Animals, Humans, Inner ear, RNA, Messenger, Zebrafish, Phylogeny, fungi, Embryogenesis, Cell Membrane, Gene Expression Regulation, Developmental, Zebrafish Proteins, biology.organism_classification, Phenotype, Molecular biology, Sensory Systems, Reverse transcription polymerase chain reaction, Connexin 26, medicine.anatomical_structure, Ear, Inner, Gene Knockdown Techniques, embryonic structures, Models, Animal, HeLa Cells
Abstract

The intercellular gap junction channels formed by connexins (CXs) are important for recycling potassium ions in the inner ear. CXs are encoded by a family of the CX gene, such as GJB2 , and the mechanism leading to mutant connexin-associated diseases, including hearing loss, remains to be elucidated. In this study, using bioinformatics, we found that two zebrafish cx genes, cx27.5 and cx30.3 , are likely homologous to human and mouse GJB2 . During embryogenesis, zebrafish cx27.5 was rarely expressed at 1.5–3 h post-fertilization (hpf), but a relatively high level of cx27.5 expression was detected from 6 to 96 hpf. However, zebrafish cx30.3 transcripts were hardly detected until 9 hpf. The temporal experiment was conducted in whole larvae. Both cx27.5 and cx30.3 transcripts were revealed significantly in the inner ear by reverse transcription polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization (WISH). In the HeLa cell model, we found that zebrafish Cx27.5 was distributed intracellularly in the cytoplasm, whereas Cx30.3 was localized in the plasma membrane of HeLa cells stably expressing Cx proteins. The expression pattern of zebrafish Cx30.3 in HeLa cells was more similar to that of cells expressing human CX26 than Cx27.5. In addition, we found that Cx30.3 was localized in the cell membrane of hair cells within the inner ear by immunohistochemistry (IHC), suggesting that zebrafish cx30.3 might play an essential role in the development of the inner ear, in the same manner as human GJB2 . We then performed morpholino knockdown studies in zebrafish embryos to elucidate the physiological functions of Cx30.3. The zebrafish cx30.3 morphants exhibited wild-type-like and heart edema phenotypes with smaller inner ears at 72 hpf. Based on these results, we suggest that the zebrafish Cx30.3 and mammalian CX26 may play alike roles in the inner ear. Thus, zebrafish can potentially serve as a model for studying hearing loss disorders that result from human CX26 mutations.

Published
2013

33. Risk of retinal vein occlusion in patients with systemic lupus erythematosus: a population-based cohort study

Author

Shih-Feng Weng, Yung Chang Yen, Horng An Chen, and Yong-Song Lin

Subjects
Adult, Male, medicine.medical_specialty, Retinal Vein, Adolescent, Population, Taiwan, Cohort Studies, Cellular and Molecular Neuroscience, Young Adult, Age Distribution, immune system diseases, Risk Factors, Internal medicine, Epidemiology, Occlusion, Retinal Vein Occlusion, medicine, Humans, Lupus Erythematosus, Systemic, In patient, Risk factor, Sex Distribution, skin and connective tissue diseases, education, Child, Aged, Proportional Hazards Models, Retrospective Studies, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Infant, Middle Aged, Sensory Systems, Surgery, Ophthalmology, Child, Preschool, Female, business, Cohort study
Abstract

Background/aims To investigate the risk of developing retinal vein occlusion (RVO) in patients with systemic lupus erythematosus (SLE). Methods In this retrospective population-based cohort study, 6756 patients with SLE and 40 536 controls without SLE (1:6) were selected from the Taiwan National Health Insurance Research Database claims from 2001 to 2006. Results The incidence of RVO was 3.46-times higher in the SLE group than in controls (5.61 vs 1.62 per 10 000 person-years) (adjusted HR=3.883, 95% CI 2.299 to 6.558) calculated using Cox proportional hazard regression. Age was an independent risk factor for RVO, with adjusted HRs of 4.842 for individuals aged ≥50 years compared with those 0–49 years. For each age subgroup, the risk of RVO was significantly higher only in the 0–49-year-old SLE group than in controls. In the 0–49-year-old SLE group the incidence of developing RVO was 7.92 times higher (95% CI 3.60 to 17.45) in the SLE group than in the 0–49-year-old controls. In women with SLE, the incidence of developing RVO was 3.33-times higher (95% CI 1.88 to 5.90) than in female controls. Conclusions SLE was significantly associated with an increased risk of developing RVO.

Published
2013

34. X-box binding protein 1 (XBP1) C−116G polymorphisms in bipolar disorders and age of onset

Author

Shih-Jen Tsai, Sheue-Jane Hou, Chen-Jee Hong, Chih-Ya Cheng, and Feng-Chang Yen

Subjects
Adult, Male, X-Box Binding Protein 1, Bipolar Disorder, XBP1, Genotype, Regulatory Factor X Transcription Factors, Biology, Pathogenesis, Gene Frequency, medicine, Humans, Point Mutation, Bipolar disorder, Age of Onset, Family history, Allele frequency, Genetics, Polymorphism, Genetic, General Neuroscience, Nuclear Proteins, Promoter, Middle Aged, medicine.disease, DNA-Binding Proteins, Case-Control Studies, Female, Age of onset, Transcription Factors
Abstract

X-box binding protein 1(XBP1), a critical gene in the endoplasmic reticulum stress response, is located on chromosome 22q12, which has been linked with bipolar disorders in several studies. Recently, associations have been reported between a polymorphism ( −116C → G) in the promoter region of XBP1, and bipolar disorders in both case-control study and family-based association study, however, this finding is not yet confirmed by other research using independent sample populations. To replicate this finding and determine the association between onset age of bipolar disorders and the XBP1 C−116G polymorphism, we investigated the prevalence of this polymorphism in a Chinese population (153 bipolar disorder patients and 174 controls). We were unable, however, to demonstrate a significant association between the C −116G polymorphism and bipolar disorders (P = 0.674 for genotype and P = 0.436 for allele frequency) or age at onset (P = 0.563). Further, no association was demonstrated between this polymorphism and family history in bipolar disorder patients. These negative findings suggest that the XBP1 C−116G polymorphism does not play a major role in the pathogenesis of bipolar disorders in Chinese populations. © 2004 Elsevier Ireland Ltd. All rights reserved.

Published
2004

35. The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma

Author

Chih-Chen Hong, Shiu-Feng Huang, Hong-Dar Isaac Wu, Hock-Liew Eng, Cheng-Chung Tsai, Il-Chi Chang, Cheng-Hsiang Hsiao, Tseng-Chang Yen, Chi-Ling Chen, Yun-Fan Liaw, Chuan-Mo Lee, Gin-Ho Lo, Hui-Hwa Tseng, Pei-Jer Chen, Chao-Long Chen, John Wang, Chau-Ting Yeh, Hsien-Chung Yu, Po-Huang Lee, Miin-Fu Chen, and Cheng-Chung Wu

Subjects
Adult, Liver Cirrhosis, Male, Hepatitis B virus, medicine.medical_specialty, HBsAg, Carcinoma, Hepatocellular, Hepatitis C virus, Taiwan, Observational Study, Hepacivirus, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Aged, Hepatitis, Hepatitis B Surface Antigens, business.industry, Data Collection, Liver Neoplasms, Age Factors, virus diseases, General Medicine, Hepatitis C, Middle Aged, Hepatitis B, medicine.disease, digestive system diseases, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, DNA, Viral, Female, 030211 gastroenterology & hepatology, business, Viral hepatitis, Research Article
Abstract

Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research.

Published
2016

36. Polymorphisms in LMNA and near a SERPINA13 gene are not associated with cognitive performance in Chinese elderly males without dementia

Author

Ying Jay Liou, Heng Liang Yeh, Feng Chang Yen, Shih-Jen Tsai, Mu En Liu, Chen-Jee Hong, Sheue Jane Hou, and Albert C. Yang

Subjects
Gerontology, Male, Aging, Neuropsychological Tests, Affect (psychology), LMNA, Cognition, Asian People, medicine, Memory span, Dementia, Humans, Effects of sleep deprivation on cognitive performance, Genetic Association Studies, Serpins, Aged, Aged, 80 and over, Mini–Mental State Examination, Polymorphism, Genetic, medicine.diagnostic_test, General Neuroscience, Wechsler Adult Intelligence Scale, Middle Aged, medicine.disease, Lamin Type A, Psychology
Abstract

Aging is associated with cognitive deterioration. A recent study showed two polymorphisms (rs505058 in LMNA and rs11622883 near a SERPINA13 gene), identified in a genome-wide association study of late-onset Alzheimer's disease, to be associated with cognitive function (Mini Mental State Examination) in a UK elderly population. This study replicated these findings in Chinese elderly males without dementia. A total of 358 elderly subjects were assessed by the Cognitive Abilities Screening Instruments (CASI) and the Wechsler Digit Span Task tests. Analysis of covariance was used to compare cognitive scores among genotypic groups, with age and total education years as covariates. The two polymorphisms were not associated with the global cognitive function or specific cognitive domains in the elderly without dementia. Our data argue against that these two polymorphisms may affect cognitive function in the elderly.

Published
2011

37. Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

Author

Spector, Tim D., Rotimi, Charles N., Hedblad, Bo, Brand, Eva, Day, Ian N. M., Kita, Yoshikuni, Chandak, Giriraj R., Tomaszewski, Maciej, Wong, Andrew, Ogihara, Toshio, Salomaa, Veikko, Igl, Wilmar, Laitinen, Jaana, Olden, Matthias, Okamura, Tomonori, Peltonen, Leena, Witteman, Jacqueline C. M., Wichmann, H-erich, Palmer, Lyle J., Boerwinkle, Eric, Talmud, Philippa J., Tabara, Yasuharu, Platou, Carl G. P., Gyllensten, Ulf B., Meneton, Pierre, Dominiczak, Anna F., Frayling, Timothy M., Groop, Leif, Smith, Albert V., Jackson, Anne U., Kutlar, Abdullah, Heath, Simon, Voight, Benjamin F., Meitinger, Thomas, Stringham, Heather M., Gaunt, Tom R., Islam, Muhammad, Tai, E. Shyong, Hofman, Albert, Lohman, Kurt K., Rotter, Jerome I., Hoffman Bolton, Judith A., Schouw, Yvonne T., Raffel, Leslie J., Lawrence, Robert W., Rudock, Megan E., Scuteri, Angelo, Peden, John F., Eyheramendy, Susana, Aspelund, Thor, Adair, Linda S., Demirkan, Ayse, Staessen, Jan A., Glazer, Nicole L., Launer, Lenore, Ganesh, Santhi, Hirschorn, Joel N., Seshadri, Sudha, Sjo&#776, gren, Marketa, Musani, Solomon K., Verwoert, Germaine C., Umemura, Satoshi, Bis, Joshua C., Dreisbach, Albert W., Keating, Brendan J., Ala-korpela, Mika, Hartikainen, Anna-liisa, Galan, Pilar, Strachan, David P., Hadley, David, Prokopenko, Inga, Young, J. Hunter, Ehret, Georg B., Prabhakaran, Dorairajan, Scott, Laura J., Mosley, Thomas H., Viikari, Jorma, Ohkubo, Takayoshi, Wiggins, Kerri L., Emilsson, Valur, Salako, Tunde, Vo&#776, lker, Uwe, Bornstein, Stefan R., lzke, Henry, Dries, Daniel L., Sharma, Pankaj, Ueshima, Hirotsugu, Wright, Alan F., Lee, Nanette R., Loos, Ruth J. F., Lawlor, Debbie A., Kathiresan, Sekar, Cho, Yoon Shin, Luan, Jian An, Jafar, Tazeen H., Bakker, Stephan J. L., Altshuler, David, Arking, Dan E., Tayo, Bamidele O., Smith, George Davey, Liu, Kiang, Taylor, Herman A., Parsa, Afshin, Mattace-raso, Francesco U. S., Wild, Sarah H., Guo, Xiuqing, Shuldiner, Alan R., Zhang, Weihua, Zhang, Feng, Harris, Tamara B., Kuusisto, Johanna, Zukowska-szczechowska, Ewa, Nyberg, Fredrik, Vineis, Paolo, Dahgam, Santosh, Hayward, Caroline, Hicks, Andrew A., Kuh, Diana, Shriner, Daniel, Taylor, Andrew, Mckenzie, Colin A., Wang, Thomas J., Steinle, Nanette I., Elosua, Roberto, Sim, Xueling, Kang, Sun J., Rivadeneira, Fernando, Palmen, Jutta, Cooper, Matthew N., Lyon, Helen N., Levy, Daniel, Swift, Amy J., Raitakari, Olli, Lyytika&#776, inen, Leo-pekka, Saleheen, Danish, Rudan, Igor, Schwarz, Peter E. H., Kooner, Jaspal S., Smith, Nicholas L., Matullo, Giuseppe, Barroso, Ine&#770, s, O Connell, Jeffrey R., Hunt, Steven C., Hernandez, Dena, Erdmann, Jeanette, Wu&#776, rz, Peter, Forrester, Terrence, Burton, Paul R., Ongen, Halit, Bandinelli, Stefania, Thelle, Dag S., Sehmi, Joban S., O Reilly, Paul F., Braund, Peter S., Danesh, John, Wyatt, Sharon B., Parker, Alex N., Polak, Josef F., Collins, Rory, Zhao, Jing Hua, Shi, Gang, Dehghan, Abbas, Rosengren, Annika, Whincup, Peter H., Duijn, Cornelia M., Hwang, Shih-jen, Ridker, Paul M., Chakravarti, Aravinda, Uda, Manuela, Tanaka, Toshiko, Pramstaller, Peter P., Morken, Mario A., Soininen, Pasi, Abecasis, Gonc&#807, alo R., Zhai, Guangju, Curb, J. David, Ferrucci, Luigi, Doumatey, Ayo P., Fox, Ervin R., Bergman, Richard N., Johnson, Toby, Larson, Martin G., Snieder, Harold, Morris, Richard W., Onland-moret, N. Charlotte, Johnson, Andrew D., Narisu, Narisu, Samani, Nilesh J., Pihur, Vasyl, Chaturvedi, Nish, Melander, Olle, Hamsten, Anders, Charchar, Fadi J., Ludwig, Barbara, Kim, Hyung-lae, Bergmann, Sven, Nalls, Michael A., Milaneschi, Yuri, Palmer, Nicholette D., Alexander, Myriam, Townsend, Raymond R., Caulfield, Mark J., Hilton, Gina, Tuomilehto, Jaakko, Lee, Jong-young, Perola, Markus, Grobbee, Diederick E., Longstreth, Will T., Munroe, Patricia B., Uitterlinden, Andre G., Iwai, Naoharu, Adeyemo, Adebowale, Cooper, Richard S., Mcardle, Wendy L., Sun, Yan V., Sijbrands, Eric J. G., Fabsitz, Richard R., Nguyen, Khanh-dung Hoang, Martin, Lisa W., Wareham, Nicholas J., Brown, Morris J., Wang, Xiaoling, Kuznetsova, Tatiana, Rao, Dabeeru C., Org, Elin, Gilst, Wiek H., Orru, Marco, Oostra, Ben A., Howard, Philip, Wagenknecht, Lynne E., Meschia, James F., Mooser, Vincent, Lehtima&#776, ki, Terho, Wong, Tien Y., Langefeld, Carl D., Bragg-gresham, Jennifer L., Bochud, Murielle, Arora, Pankaj, Kivimaki, Mika, Seielstad, Mark, O Donnell, Chris, Chasman, Daniel I., Farrall, Martin, Polasek, Ozren, Fava, Cristiano, Vitart, Veronique, Mani, K. Radha, Uiterwaal, Cuno S. P. M., Chang, Yen-pei C., Zhu, Haidong, Morrison, Alanna C., Bonnycastle, Lori L., Najjar, Samer, Vollenweider, Peter, Eaton, Charles B., Singleton, Andrew, Teumer, Alexander, Deloukas, Panos, Campbell, Harry, Terzic, Janos, Aulchenko, Yurii, Farlow, Deborah N., Psaty, Bruce M., Beckmann, Jacques S., Scott, James, Tobin, Martin D., Kao, Wen Hong Linda, Harst, Pim, Amin, Najaf, Zitting, Paavo, Pattaro, Cristian, Casas, Juan P., Ikram, M. Arfan, Coresh, Josef, Hingorani, Aroon D., Kulkarni, Smita R., Shrine, Nick R. G., Yao, Jie, Fowkes, F. Gerald R., Clarke, Robert, Gra&#776, ssler, Ju&#776, rgen, Hercberg, Serge, Wain, Louise V., Redline, Susan, Isaacs, Aaron, Hopewell, Jemma C., Lathrop, Mark, Vinay, D. G., Marmot, Michael G., Laan, Maris, Rasheed, Asif, So&#771, ber, Siim, Vartiainen, Erkki, Han, Bok-ghee, Rettig, Rainer, Kinra, Sanjay, Artigas, Maria Soler, Veldre, Gudrun, Navis, Gerjan, Shaw-hawkins, Sue, Franceschini, Nora, Lucas, Gavin, Penman, Alan D., Ong, Rick Twee-hee, Mohlke, Karen L., Beilby, John P., Zhu, Xiaofeng, Bots, Michiel L., Chen, Ming-huei, Denniff, Matthew, Brand, Stefan-martin, Kangas, Antti J., Hveem, Kristian, Chambers, John C., Tukiainen, Taru, Boehnke, Michael, Ramachandran, Vasan S., Connell, John M., Collins, Francis S., Khaw, Kay-tee, Nilsson, Peter, Wilson, James F., Yajnik, Chittaranjan S., Guarrera, Simonetta, Gieger, Christian, Elliott, Paul, Plump, Andrew, Ricceri, Fulvio, Tzoulaki, Ioanna, Garcia, Melissa, Ka&#776, ho&#776, nen, Mika, Laakso, Markku, Kumari, Meena, Stanca&#769, kova&#769, Alena, Corsi, Anna Maria, Soranzo, Nicole, Kettunen, Johannes, Gudnason, Vilmundur, Kardia, Sharon L. R., Hardy, Rebecca, Lakatta, Edward G., Goel, Anuj, Liu, Yongmei, Dong, Yanbin, Humphries, Steve E., Rice, Kenneth M., Newton-cheh, Christopher, Ko&#776, ttgen, Anna, Viigimaa, Margus, Tripathy, Vikal, Mangino, Massimo, Janipalli, Charles S., Heckbert, Susan R., Palmas, Walter, Watkins, Hugh, Do&#776, rr, Marcus, Kroemer, Heyo K., Weder, Alan B., Wu, Ying, Schwartz, Steven M., Miki, Tetsuro, Zelenika, Diana, Cooper, Jackie A., Kumar, M. J. Kranthi, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), Ja&#776, rvelin, Marjo-riitt, EchoGen consortium, CARDIoGRAM consortium, CKDGen consortium, Charge-hf, Consortium, KidneyGen consortium, Medical Research Council (MRC), Kuznetsova, Tatiana, Staessen, Jan A, Pediatrics, Ehret, Georg Benedikt, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), CARDIoGRAM consortium, CKDGen consortium, KidneyGen consortium, EchoGen consortium, CHARGE-HF consortium, Morrison, Alanna C [0000-0001-6381-4296], Ramachandran, Vasan S [0000-0001-7357-5970], Adeyemo, Adebowale [0000-0002-3105-3231], Martin, Lisa W [0000-0003-4352-0914], Caulfield, Mark J [0000-0001-9295-3594], Levy, Daniel [0000-0003-1843-8724], Apollo - University of Cambridge Repository, Epidemiologie, and RS: CARIM School for Cardiovascular Diseases

Subjects
Male, Candidate gene, Blood pressure, GWAS, genetic variant, African Americans, Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, Cardiovascular, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, Diastole, 2.1 Biological and endogenous factors, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), European Continental Ancestry Group/genetics, Aetiology, International HapMap Project, International Consortium for Blood Pressure Genome-wide Association Studies, Genetics (clinical), ddc:616, Genetics, Genetics & Heredity, 0303 health sciences, Association Studies Articles, Single Nucleotide, General Medicine, 11 Medical And Health Sciences, Biological Sciences, Middle Aged, 3. Good health, Phenotype, Hypertension, Female, Adult, Genotype, Systole, European Continental Ancestry Group, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, White People, genome-wide association, hypertension prevalence, receptor, disease, family, loci, vasculature, awareness, traits, design, 03 medical and health sciences, Clinical Research, Genetic variation, Humans, Genetic variability, Polymorphism, Hypertension/epidemiology/genetics, Molecular Biology, 030304 developmental biology, Genetic association, Aged, African Americans/genetics, Human Genome, 06 Biological Sciences, Black or African American, Genetic Loci, Genome-Wide Association Study, Hypertension/epidemiology, Hypertension/genetics, Imputation (genetics)
Abstract

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. ispartof: HUMAN MOLECULAR GENETICS vol:20 issue:11 pages:2273-2284 ispartof: location:England status: published

Published
2011

38. Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response

Author

Chen-Jee Hong, Sheue-Jane Hou, Tai-Jui Chen, Younger W.-Y. Yu, Ying-Jay Liou, Shih-Jen Tsai, and Feng-Chang Yen

Subjects
Adult, Male, Genotype, Serotonin reuptake inhibitor, Taiwan, Citalopram, Pharmacology, Tryptophan Hydroxylase, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Gene Frequency, Fluoxetine, mental disorders, medicine, Humans, Genetic Predisposition to Disease, Biological Psychiatry, Depressive Disorder, Major, TPH2, Middle Aged, medicine.disease, Antidepressive Agents, Major depressive disorder, Antidepressant, Female, Reuptake inhibitor, Psychology, Pharmacogenetics, Selective Serotonin Reuptake Inhibitors, medicine.drug
Abstract

Tryptophan hydroxylase-2 (TPH2) is the rate-limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to investigate whether common genetic variation in the TPH2 gene is associated with MDD and therapeutic response to antidepressants in a Chinese population. A total of 508 MDD patients and 463 unrelated controls were recruited. Among the MDD patients, 187 accepted selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressant treatment for 8 weeks with therapeutic evaluation before and after treatment. Five TPH2 polymorphisms were genotyped and their association with MDD or treatment response was assessed by haplotype and single-marker analysis. In single-marker-based analysis, the rs17110747-G homozygote polymorphism was found to be more frequent in the MDD patients than in the controls (P=0.002). Genotype analysis in responders (defined as those with a 50% reduction in baseline Hamilton score) and non-responders after 8 weeks of antidepressant treatment showed that the proportion of rs2171363 heterozygote carriers was higher in the responders than the non-responders (P=0.009). No significant association with MDD or antidepressant therapeutic response was discovered in haplotype analyses. Our findings show that TPH2 genetic variants may play a role in MDD susceptibility and in acute therapeutic response to selective serotonin reuptake inhibitors.

Published
2008

39. Spike sorting by a minimax reduced feature set based on finite differences

Author

Meng Li Tsai, Chien Chang Yen, Chen-Tung Yen, and Wei Chang Shann

Subjects
Principal Component Analysis, Quantitative Biology::Neurons and Cognition, Physiology, business.industry, Models, Neurological, Sorting, Finite difference, Action Potentials, Pattern recognition, Signal Processing, Computer-Assisted, Minimax, Electrophysiology, Wavelet, Spike sorting, Principal component analysis, Animals, Humans, Spike (software development), Artificial intelligence, Feature set, business, Algorithms, Mathematics
Abstract

Spikes are classified according to their finite differences in various orders. The fundamental idea that makes it work is that finite differences can extract and isolate features from spikes. This method showed better sorting quality and involved less labor than the methods of principal component analysis, original reduced feature set, and wavelet-based spike classifiers.

Published
2008

40. Is dysfunction of the tissue plasminogen activator (tPA)-plasmin pathway a link between major depression and cardiovascular disease?

Author

Feng-Chang Yen, Shih-Jen Tsai, and Sheue-Jane Hou

Subjects
medicine.medical_specialty, Plasmin, Inflammation, Disease, Bioinformatics, behavioral disciplines and activities, Tissue plasminogen activator, Pathogenesis, Neurotrophic factors, Internal medicine, mental disorders, medicine, Humans, Fibrinolysin, Depressive Disorder, Major, Brain, General Medicine, medicine.disease, Endocrinology, Cardiovascular Diseases, Tissue Plasminogen Activator, Major depressive disorder, medicine.symptom, Psychology, Plasminogen activator, medicine.drug
Abstract

Epidemiological, genetic and clinical studies have demonstrated an association between major depressive disorder (MDD) and cardiovascular disease (CVD). For example, MDD is a risk factor for the development of CVD, while around one fifth of patients with CVD have MDD and a significantly larger percentage have subsyndromal symptoms of depression. Furthermore, patients with CVD and depression have an increased risk of future cardiac events compared to similar cohorts without depression, independent of baseline cardiac dysfunction. Despite evidence that CVD and MDD are epidemiologically linked, the cause of this correlation is still unknown. Several risk factors including physical and psychological stress, smoking, physical inactivity and inflammation have been proposed to mediate the interaction between MDD and CVD. The tissue-type plasminogen activator (tPA)-plasminogen proteolytic cascade is widely expressed in the brain. Accumulating evidence from preclinical and clinical studies suggests that tPA and its inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. In addition, brain-derived neurotrophic factor (BDNF) is important for the pathogenesis of MDD and the tPA-plasminogen proteolytic cascade has been implicated in the cleavage of proBDNF to BDNF in the brain, by which the direction of BDNF action is controlled. Thus, it is proposed that tPA-plasmin pathway dysfunction may play a role in the link between MDD and CVD. Future study of the components in the tPA-plasminogen system in CVD patients comorbid with MDD may lead to new, potentially important insights into the link between MDD and CVD, and might also contribute to novel strategies for the management of these two common and devastating diseases.

Published
2008

41. Interleukin-1 beta (C-511T) genetic polymorphism is associated with cognitive performance in elderly males without dementia

Author

Cheng-Hsi Hsieh, Chen-Jee Hong, Ying-Jay Liou, Sheue-Jane Hou, Shih-Jen Tsai, Mu-En Liu, and Feng-Chang Yen

Subjects
Oncology, Male, medicine.medical_specialty, Aging, Apolipoprotein E4, Interleukin-1beta, Neuropsychological Tests, Polymorphism, Single Nucleotide, Statistics, Nonparametric, Cognition, Polymorphism (computer science), Reference Values, Internal medicine, Post-hoc analysis, medicine, Memory span, Dementia, Humans, Effects of sleep deprivation on cognitive performance, Cognitive decline, Aged, Genetics, Aged, 80 and over, General Neuroscience, Wechsler Adult Intelligence Scale, medicine.disease, Cross-Sectional Studies, Neurology (clinical), Geriatrics and Gerontology, Psychology, Developmental Biology
Abstract

Interleukin-1 beta (IL-1 beta), a proinflammatory cytokine, plays a significant role in age-related changes in long-term potentiation (a biological substrate for learning and/or memory) in the hippocampus of experimental animals. This study tests the hypothesis that a biallelic functional polymorphism in the promoter region (position-511) (rs16944) of the IL-1 beta gene is associated with cognitive performance in elderly males without dementia. A total of 161 elderly male subjects without major psychiatric disorders or dementia participated in this research. Cognitive functions were assessed by the Cognitive Abilities Screening Instruments (CASI) test as well as The Wechsler Digit Span Task test. A significant association was found between the IL-1 beta C-511T polymorphism and CASI score (p = 0.008), particularly in the abstraction and judgment subtest (p = 0.010), and the backward digit span test (p = 0.004). Post hoc tests indicated that the C/C genotype gained better cognitive function test results than T/T carriers, mainly in the non-apolipoprotein E allele epsilon 4 carriers. These results suggest that genetic variants of the IL-1 beta C-511T polymorphism may play a role in specific cognitive functions in normal aged males. Considering that cognitive decline in the elderly is associated with local inflammation processes, genetic variants of cytokines and their receptors should be tested to improve gene-based prediction of general cognitive function in the elderly.

Published
2008

42. Identification of mutations in the myocilin (MYOC) gene in Taiwanese patients with juvenile-onset open-angle glaucoma

Author

Yung-Chang, Yen, Jiann-Jou, Yang, Ming-Chih, Chou, and Shuan-Yow, Li

Subjects
Polymorphism, Genetic, Base Sequence, Adenine, Mutation, Missense, Taiwan, Middle Aged, Introns, Cytoskeletal Proteins, Asian People, Codon, Nonsense, Mutation, Humans, Age of Onset, Eye Proteins, 3' Untranslated Regions, Glaucoma, Open-Angle, Thymine, Glycoproteins
Abstract

To investigate mutations in the promoter and coding regions of the myocilin (MYOC) gene in Taiwanese patients suffering from juvenile-onset open-angle glaucoma (JOAG).MYOC was analyzed for mutations in 48 unrelated Taiwanese probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted from peripheral blood leukocytes and then subjected to PCR to amplify exons, flanking introns and promoter regions of the MYOC gene. The amplified products were screened for base mutations by autosequence. Data from the two groups were then compared using the chi(2) test. Finally, the levels of MYOC transcripts were predicted by a neural network prediction system to study whether the intron mutations have any effect on the level of mRNA expression.The analysis revealed four MYOC mutations and six polymorphisms. The prevalence of MYOC gene mutations in this study was 12.5% (6/48). The mutations included one nonsense mutation (Arg46Stop; 3/6), one missense mutation (Val56Ala; 1/6), one intron mutation (c.604+228AT; 1/6) as well as one mutation in the 3'-untranslated region (c.1515+73GC; 1/6). In addition, although c.604+228AT is an intron mutation and does not alter the content of the amino acid residue, the neural network prediction system revealed that it can potentially create a novel accept splice site during transcription. This mutation might affect the protein structure and consequently the normal function of myocilin.Our results indicate that the c.136CT (Arg46Stop), c.158TC (Val56Ala), c.604+228AT, and c.1515+73GC mutations of MYOC may be associated with JOAG. In addition, we suggest that the c.136CT (Arg46Stop) mutation of MYOC is a hot spot in Taiwanese patients with JOAG.

Published
2007

43. Paralytic shellfish poisoning (PSP) in Margarita Island, Venezuela

Author

La Barbera-Sánchez, A., Soler, J. F., Luisa Rojas de Astudillo, and Chang-Yen, I.

Subjects
Time Factors, saxitoxin, saxitoxina, Disease Outbreaks, Gymnodinium catenatum, Animals, Humans, Shellfish Poisoning, lcsh:QH301-705.5, Alexandrium tamarense, Chromatography, High Pressure Liquid, Shellfish, Dinoflagelado, Dinoflagellate, intoxicación paralizante por moluscos, Ciguatera Poisoning, Prorocentrum, Eutrophication, Venezuela, Saxitoxinp, Paralytic Shellfish Poisoning, Bivalvia, Rats, lcsh:Biology (General), Epidemiological Monitoring, Dinoflagellida, Environmental Monitoring, Saxitoxin
Abstract

10 páginas, 4 figuras, 1 tabla, [EN] A severe outbreak of Paralytic Shellfish Poisoning (PSP) occurred in Manzanillo and Guayacán, northwestern coast of Margarita Island, Venezuela, between August and October 1991. A bloom of dinoflagellates including Prorocentrum gracile, Gymnodinium catenatum and Alexandrium tamarense seemed to be responsible for this outbreak. Levels of PSP toxins in mussels (Perna perna) exceeded the international safety limit of saxitoxin, 80 microg STX/100 microg meat. PSP toxin values varied between 2548 and 115 microg STX/100 g meat in Manzanillo, and between 1422 and 86 microg STX/100 g meat in Guayacán. At both locations, the highest levels were detected in August, when 24 patients exhibited typical symptoms of PSP toxicity after consuming cooked mussels (16 required hospitalization). A high pressure liquid chromatographic (HPLC) procedure was recently used on the 1991 samples. The major toxin detected in samples of both locations was decarbamoyl saxitoxin (dcSTX), but low concentrations of saxitoxin were also found in Manzanillo samples. Gonyautoxins GTX1, GTX2 and GTX3 were detected only at Guayacán, while in both locations, decarbamoylgonyatouxin (dcGTX2,3) toxins were detected. These findings represent the first time that causative toxins of PSP in Venezuela have been chemically identified, and confirm the presence of dcSTX and dcGTX in mussels from the Caribbean Sea. The presence of dcSTX and dcGTX in shellfish is indicative that Gymnodinium catenatum was a causative organism for outbreak of PSP., [ES] Un severo brote de intoxicación paralizante por moluscos (PSP en inglés) ocurrió en Manzanillo y Guayacán en la costa noroeste de la Isla de Margarita, Venezuela entre agosto y octubre de 1991. Una proliferación de Prorocentrum gracile, Gymnodinium catenatum y Alexandrium tamarense causó el brote. Los niveles de PSP en mejillón (Perna perna) superaron los niveles máximos permisibles de saxitoxina, 80 µg STX/100g carne. Los niveles de toxinas variaron entre 2 548 y 115 µg STX/100 g carne en Manzanillo y entre 1 422 y 86 µg STX/100g carne en Guayacán. En ambas localidades, los máximos niveles se detectaron en agosto, cuando 24 personas presentaron síntomas típicos de PSP después de consumir mejillones cocidos (16 fueron hospitalizados). Se aplicó recientemente cromatografía líquida de alta presión (HPLC) a muestras del año 1991 y la toxina más detectada fue decarbamoyl saxitoxina (dcSTX), pero también se encontró saxitoxinas en muestras de Manzanillo. Las gonyautoxinas GTX1, GTX2 y GTX3 solo se encontraron en Guayacán; en ambas localidades se detectó decarbamoylgonyatouxin (dcGTX2,3). Estos hallazgos representan la primera vez que las toxinas causantes de un brote de PSP en Venezuela han sido químicamente identificadas, confirmando la presencia de dcSTX y dcGTX en mejillones del mar Caribe. La presencia de dcSTX y dcGTX en moluscos, indica que G. catenatum fue el organismo responsable de la intoxicación., We acknowledge the support of Technological Development Program, phase II, subscribed between Venezuelan Government and the Interamerican Development Bank, Instituto de Oceanografia, Spain, Intergovernmental Oceanographic Commision (IOC) of UNESCO, Consejo de Investigación of Universidad de Oriente, Venezuela, and The University of the West Indies, Trinidad.

Published
2007
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44. Heavy metals in sediments, mussels and oysters from Trinidad and Venezuela

Author

L Rojas de, Astudillol, I Chang, Yen, and I, Bekele

Subjects
Geologic Sediments, Principal Component Analysis, Sewage, Spectrophotometry, Atomic, Industrial Waste, Mercury, Venezuela, Ostreidae, Bivalvia, Trinidad and Tobago, Reference Values, Metals, Heavy, Animals, Humans, Shellfish Poisoning, Biomarkers, Water Pollutants, Chemical, Environmental Monitoring
Abstract

The Gulf of Paria is bordered by both Trinidad and Venezuela, from which various metallic pollutants and other contaminants can originate. The Gulf is still a significant source of fish, crabs and shellfish for human consumption to both countries, where concerns over the quality of this marine environment have been long expressed but never properly addressed. In addition, the circulatory current patterns in the Gulf ensure that contaminants originating from either country are likely to affect both countries eventually. Heavy metals were determined in oysters (Crassostrea rhizophorae and C. virginica), green mussels (Perna viridis) and sediments from the Gulf of Paria. Samples were obtained at four sites in Trinidad and three sites in Venezuela in the Gulf of Paria, in addition to comparative samples collected from three sites on the north coast of Venezuela. Edible tissues of twelve shellfish from each location were blended and aliquots digested with concentrated nitric acid, for extraction of cadmium, chromium, copper, lead, nickel and zinc. The solutions were analysed by flame atomic absorption spectroscopy. Mercury was extracted with a mixture of nitric, hydrochloric and sulphuric acids and determined by cold vapour atomic absorption. Sediments were oven-dried at 60'C, before being similarly extracted. Results showed that mercury in sediments at all sites in Trinidad and Venezuela exceeded NOAA and Canadian sediment quality guidelines, while cadmium, copper, nickel, lead and zinc also exceeded these guidelines at several sites. Heavy metal levels in oysters and green mussels varied widely with location. However, oysters from the Gulf of Paria contained significantly higher mean levels of cadmium, copper, nickel and zinc than those from the north coast of Venezuela, but this difference was not apparent in mussels. Cadmium, mercury and zinc in sediments were significantly correlated with those of mussels, but not of oysters, in which copper and zinc at several sites in the Gulf of Paria exceeded local maximum permissible levels (Cu = 20 microg g(-1) wet wt; Zn = 50 microg g(-1) wet wt) for human consumption. These findings indicate that while mussels may be better biological indicators of heavy metal pollution in sediments than oysters, the latter may provide copper and zinc contamination. Further research is needed to determine the most appropriate biological indicators of heavy metal and other pollutants in the local marine environment and to develop protocols for their use.

Published
2007

45. Association study of polymorphisms in the mitochondrial aspartate/glutamate carrier SLC25A12 (aralar) gene with schizophrenia

Author

Shih-Jen Tsai, Ying-Jay Liou, Feng-Chang Yen, Ding-Lieh Liao, Sheue-Jane Hou, and Chen-Jee Hong

Subjects
Adult, Male, Psychosis, Linkage disequilibrium, Genotype, Locus (genetics), Mitochondrion, Mitochondrial Membrane Transport Proteins, Linkage Disequilibrium, Mitochondrial Proteins, mental disorders, medicine, Glutamate aspartate transporter, Humans, Gene, Biological Psychiatry, Pharmacology, Genetics, Brain Chemistry, Aspartic Acid, Polymorphism, Genetic, biology, Haplotype, Glutamate receptor, Membrane Transport Proteins, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Haplotypes, Case-Control Studies, biology.protein, Schizophrenia, Female
Abstract

Aralar is a mitochondrial calcium-regulated aspartate-glutamate carrier mainly distributed in brain and skeletal muscle, and involved in the transport of aspartate from mitochondria to the cytosol of a cell. Studies have shown that the brain N-acetyl aspartate (NAA) levels are greatly decreased in aralar-deficient mice, suggesting that aralar plays an important role in the synthesis of NAA in neuronal cells. Since magnetic resonance spectroscopy studies have revealed consistently reduced NAA levels in various brain regions of schizophrenic patients and their unaffected relatives, genes that affect aralar levels or NAA metabolism in the brain may be implicated in the pathogenesis of schizophrenia. Aralar is encoded by the SLC25A12 gene. In the past this gene has been found to be associated with susceptibility to autism; in this study we tested the hypothesis that SLC25A12 genetic variants confer susceptibility to schizophrenia. Six SLC25A12 polymorphisms were studied in a sample population of 253 people with schizophrenia and 216 normal controls. Significant linkage disequilibrium was obtained among the six polymorphisms. However, neither single marker nor haplotype analysis revealed an association between variants at the SLC25A12 locus and schizophrenia, suggesting that it is unlikely that the SLC25A12 polymorphisms investigated play a substantial role in conferring susceptibility to schizophrenia in the Chinese population. Further studies with SLC25A12 variants relating to brain NAA levels in patients with schizophrenia are suggested.

Published
2007

46. Family-based association study between G72/G30 genetic polymorphism and schizophrenia

Author

Shih-Jen Tsai, Sheue-Jane Hou, Chen-Jee Hong, Feng-Chang Yen, and Ying-Jay Liou

Subjects
Proband, Adult, Male, Psychosis, DNA Mutational Analysis, Biology, Population stratification, Linkage Disequilibrium, Sex Factors, Polymorphism (computer science), mental disorders, Genetic variation, medicine, Odds Ratio, Humans, RNA, Messenger, Allele, Genetics, Family Health, Chi-Square Distribution, Polymorphism, Genetic, General Neuroscience, Confounding, Intracellular Signaling Peptides and Proteins, Proteins, medicine.disease, Schizophrenia, Case-Control Studies, Female, Carrier Proteins
Abstract

Genetic variations in G72/G30 have been reported to be associated with schizophrenia and bipolar disorders in several case- control studies. This gene is located in a genomic region known to contain susceptibility genes for schizophrenia. As case-control studies carry an increased risk of confounding through population stratification, we investigate whether the rs947267 (A/C) polymorphism is associated with schizophrenia in a family-based association study. This polymorphism is located within the G72/G30 gene and has been previously associated with bipolar disorders. The sample consisted of a total of 216 Chinese families that included an affected offspring and parents. Transmission disequilibrium analysis revealed a significant association between the G72/G30 rs947267 polymorphism and schizophrenia (P=0.016), with the A allele more commonly transmitted to patients. Further analysis stratified by sex showed that the A allele was significantly more overtransmitted than nontransmitted in the trios of male probands (P=0.031), but not in the trios of female probands. Our family-based association study supports the suggestion that the G72/G30 gene may be implicated in susceptibility to schizophrenia and there may be an interaction between this gene and sex in the pathogenesis of schizophrenia.

Published
2006

47. Gray-scale and color Doppler ultrasonographic manifestations of papillary thyroid carcinoma: analysis of 51 cases

Author

Yi-Hong Chou, Chang-Yen Cheng, Chen-Hsen Lee, Chui-Mei Tiu, Hong-Jen Chiou, Hui-Chen Hsu, and Wei-Hsin Yuan

Subjects
Adult, Male, medicine.medical_specialty, Sensitivity and Specificity, Thyroid carcinoma, Vascularity, Carcinoma, medicine, Humans, Radiology, Nuclear Medicine and imaging, Thyroid Neoplasms, Ultrasonography, Doppler, Color, Aged, Retrospective Studies, business.industry, Ultrasound, Echogenicity, Reproducibility of Results, Middle Aged, medicine.disease, Image Enhancement, Carcinoma, Papillary, Female, Radiology, Microcalcification, medicine.symptom, Ultrasonography, business, Calcification
Abstract

The purpose of this study is to assess the specific ultrasonic characteristics of papillary thyroid carcinoma and to determine the relative frequency of various patterns of papillary carcinoma on gray-scale ultrasonography (US) and color Doppler ultrasonography (CDU).We retrospectively reviewed US features in 51 patients with confirmed papillary thyroid carcinoma. The features were analyzed based on tumor size, echogenicity, echotexture, boundary, margin, shape, and calcification pattern on gray-scale US imaging, and on patterns of vascularity on CDU. We obtained the relative frequency of features and classified these features into three categories: common (or =50% of lesions), less common (10% but50%), and uncommon (or =10%). Individual differences and combinations of features were also analyzed.In total, 67 nodules were enrolled in our study. The sizes of 76% of nodular lesions were20.0 mm. Common US features of papillary carcinoma included: a homogeneous hypoechoic solid picture; a poorly defined boundary; an irregular margin; the absence of halo; the absence of calcifications or microcalcifications; and mixed perinodular and intranodular blood flow patterns. Less common features included: a heterogeneous hypoechoic or very hypoechoic picture; microcalcifications; a well-defined boundary; a regular margin; a halo with uneven thickness or an incomplete halo; and a taller-than-wide shape. Uncommon features included: an isoechoic picture; solid with cystic components; coarse calcifications; mixed coarse calcifications and microcalcifications; "inferno"-type blood flow; and absence of blood flow. On average, each nodule had 4.9 US features considered common, 1.8 US features considered less common, and 0.4 US feature considered uncommon. Features such as predominantly cystic composition, hyperechoic texture, and hypoechoic halo with even thickness were never found in our study. The top two common manifestations of papillary carcinoma were solid architecture and mixed perinodular and intranodular blood flow signals.All lesions in our series had a predominantly solid characteristic on gray-scale US.

Published
2006

48. Nutritional and sensory quality of stirred soursop (Annona muricata L.) yoghurt

Author

Maria Lutchmedial, Neela Badrie, Ivan Chang-Yen, and Reshma Ramlal

Subjects
Male, Corojo, Food Handling, Organoleptic, Flavour, Annona, Food Preferences, Humans, Nutritional Physiological Phenomena, Food science, Annona muricata, Aroma, biology, Chemistry, Flesh, Consumer Behavior, Focus Groups, biology.organism_classification, Yogurt, Lactobacillus, Annonaceae, Fruit, Taste, Female, Food Analysis, Food Science
Abstract

Soursops (Annona muricata L.) are highly aromatic fruits with white juicy flesh and are native to tropical North and South America. The ripe fruits are highly perishable, as they become soft and easily bruised. The objectives of the study were to incorporate soursop nectar at 0%, 5%, 10% and 15% in stirred yoghurts and to analyse the products for chemical and sensory quality. A focus group evaluated the initial yoghurts for process modifications. Yoghurts were evaluated on sensory attributes of appearance and colour, body and texture, flavour and aroma, and overall quality. Yoghurts with 10% and 15% soursop nectar had the highest (P

Published
2004

49. Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior

Author

Feng-Chang Yen, Guo-Mei Pan, Chen-Jee Hong, Chun-Liang Tung, Sheue-Jane Huo, and Shih-Jen Tsai

Subjects
Adult, Male, medicine.medical_specialty, Poison control, Methionine, Internal medicine, mental disorders, Genetic predisposition, medicine, Humans, Bipolar disorder, Age of Onset, Psychiatry, Allele frequency, Biological Psychiatry, Aged, Brain-derived neurotrophic factor, Polymorphism, Genetic, Mood Disorders, Reverse Transcriptase Polymerase Chain Reaction, Brain-Derived Neurotrophic Factor, Valine, Middle Aged, medicine.disease, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Suicide, Neuropsychology and Physiological Psychology, Mood, Endocrinology, Mood disorders, Case-Control Studies, Female, Age of onset, Psychology, Sequence Analysis
Abstract

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth factor family, has been implicated in both mood disorders and suicidal behavior. This study has examined the association between the BDNF gene Val66Met polymorphism and mood disorders, age of onset and suicidal behavior in a Chinese sample population. The genotype and allele frequencies for the BDNF gene Val66Met polymorphism did not differ comparing depression groups (total, bipolar disorder or major depression) and control subjects. Furthermore, it was not demonstrated that this BDNF polymorphism was associated with age of onset or suicidal history in our mood disorder patients. Based on these results, it seems reasonable to suggest that this polymorphism is unlikely to play a major role in the genetic susceptibility to mood disorders. Given the fact that the positive association between BDNF gene Val66Met polymorphism and bipolar disorder has only been demonstrated for a Caucasian population but not for a Japanese analog or our Chinese sample, it appears likely that this association is ethnicity dependent.

Published
2003

50. Association study of serotonin transporter gene VNTR polymorphism and mood disorders, onset age and suicide attempts in a Chinese sample

Author

Sheu-Jane Hou, Chen-Jee Hong, Shih-Jen Tsai, Feng-Chang Yen, and Jiunn-Kae Wang

Subjects
Adult, Male, Genotype, Nerve Tissue Proteins, Suicide, Attempted, Minisatellite Repeats, Bioinformatics, Asian People, Gene Frequency, Polymorphism (computer science), mental disorders, medicine, Humans, Bipolar disorder, Age of Onset, Allele frequency, Biological Psychiatry, Serotonin transporter, Genetics, Serotonin Plasma Membrane Transport Proteins, Membrane Glycoproteins, Polymorphism, Genetic, biology, Mood Disorders, Reverse Transcriptase Polymerase Chain Reaction, Membrane Transport Proteins, Middle Aged, medicine.disease, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Mood, Mood disorders, Case-Control Studies, biology.protein, Major depressive disorder, Female, Age of onset, Psychology, Carrier Proteins
Abstract

The human serotonin transporter (5-HTT) gene is an important candidate for the pathogenesis of mood disorders. Associations have been reported between a variable-number tandem-repeat polymorphism in intron 2 of the serotonin transporter gene (5-HTTVNTR) and mood disorders in a number of studies of Western and Chinese populations. However, no such relationships have been determined in other analogous research. To replicate these positive findings in a Chinese population and to determine the association between onset age of bipolar disorder and 5-HTTVNTR, we investigated the prevalence of this polymorphism in an independent Chinese population (83 bipolar disorder patients, 77 major depressive disorder patients and 169 controls), demonstrating no significant association between the 5-HTTVNTR polymorphism and mood disorders or age at onset. Further, no association was demonstrated between this polymorphism and suicidal history in mood disorder patients. These negative findings suggest that 5-HTTVNTR does not play a major role in the pathogenesis of mood disorder in Chinese populations.

Published
2003

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