Author: "Michel, G." / Topic: male - Searchworks@Jio Institute Digital Library Search Results

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217 results on '"Michel, G."'

1. Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness

Author: Abdellaoui, Abdel, Sanchez-Roige, Sandra, Sealock, Julia, Treur, Jorien L, Dennis, Jessica, Fontanillas, Pierre, Elson, Sarah, Team, The 23andme Research, Nivard, Michel G, Ip, Hill Fung, van der Zee, Matthijs, Baselmans, Bart ML, Hottenga, Jouke Jan, Willemsen, Gonneke, Mosing, Miriam, Lu, Yi, Pedersen, Nancy L, Denys, Damiaan, Amin, Najaf, van Duijn, Cornelia M, Szilagyi, Ingrid, Tiemeier, Henning, Neumann, Alexander, Verweij, Karin JH, Cacioppo, Stephanie, Cacioppo, John T, Davis, Lea K, Palmer, Abraham A, and Boomsma, Dorret I
Subjects: Biological Sciences, Genetics, Obesity, Human Genome, Mental Health, Prevention, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Cardiovascular, Mental health, Good Health and Well Being, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Health, Humans, Loneliness, Male, Mendelian Randomization Analysis, Mental Disorders, Multifactorial Inheritance, Phenomics, Phenotype, Polymorphism, Single Nucleotide, 23andme Research Team, Medical and Health Sciences, Genetics & Heredity
Abstract: Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.
Published: 2019

2. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability

Author: Pasman, Joëlle A, Verweij, Karin JH, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart ML, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, the 23andMe Research Team, de Wit, Harriet, Davis, Lea K, MacKillop, James, The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer, Jaime L, Branje, Susan JT, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol AC, Madden, Pamela AF, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, AJ, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco PM, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John RB, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, and Vink, Jacqueline M
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Prevention, Mental Health, Schizophrenia, Clinical Research, Behavioral and Social Science, Genetics, Mental Illness, Brain Disorders, Serious Mental Illness, Human Genome, Drug Abuse (NIDA only), Women's Health, Cannabinoid Research, Substance Misuse, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Cell Adhesion Molecules, Databases, Genetic, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Marijuana Abuse, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk-Taking, Young Adult, 23andMe Research Team, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Neurosciences, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.
Published: 2018

3. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.

Author: Pasman, Joëlle A, Verweij, Karin JH, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart ML, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, 23andMe Research Team, de Wit, Harriet, Davis, Lea K, MacKillop, James, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Derringer, Jaime L, Branje, Susan JT, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol AC, Madden, Pamela AF, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, AJ, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco PM, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John RB, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, and Vink, Jacqueline M
Subjects: 23andMe Research Team, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Humans, Marijuana Abuse, Genetic Predisposition to Disease, Cell Adhesion Molecules, Risk-Taking, Mental Health, Schizophrenia, Gene Expression Regulation, Genotype, Polymorphism, Single Nucleotide, Databases, Genetic, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Young Adult, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Databases, Genetic, and over, Prevention, Human Genome, Brain Disorders, Drug Abuse, Substance Abuse, Genetics, Clinical Research, 2.1 Biological and endogenous factors, Cardiovascular, Neurology & Neurosurgery, Neurosciences, Cognitive Sciences, Psychology
Abstract: Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.
Published: 2018

4. High detection rate of osteoporosis with screening of a general hospitalized population: a 6-year study in 6406 patients in a university hospital setting

Author: Olivier Malaise, Marie Detroz, Mathieu Leroy, Lorenzo Leonori, Laurence Seidel, and Michel G. Malaise
Subjects: Osteoporosis, Dual energy X-ray absorptiometry, Hospitalization, Male, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Osteoporosis is a highly prevalent disease identified by Dual Energy X-ray Absorptiometry (DEXA) that can be performed in an ambulatory (out-patient) or hospitalized population. We evaluated the use of baseline in-hospital DEXA screening to identify osteoporosis in ambulatory care and hospitalized patients; we also assessed specific risk factors for osteoporosis among these populations. Methods We included a baseline initial DEXA from 6406 consecutive patients at our tertiary referral University Hospital. Results Osteoporosis was diagnosed in 22.3% of the study population. In univariate analysis, osteoporosis risk factors were age, fracture history and low BMI (for all 3 sites), but also corticotherapy (lumbar spine and femoral neck) and male (lumbar spine). In multivariate analysis, age, fracture history, low BMI, and male increased osteoporosis risk. In-hospital screening yielded a higher percentage of osteoporosis positive scans than ambulatory care screening (31.8% vs 18.5%, p
Published: 2020
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5. Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function Following Radical Prostatectomy for Clinically Localized Prostate Cancer

Author: Jones, Lee W, Hornsby, Whitney E, Freedland, Stephen J, Lane, Amy, West, Miranda J, Moul, Judd W, Ferrandino, Michael N, Allen, Jason D, Kenjale, Aarti A, Thomas, Samantha M, Herndon, James E, Koontz, Bridget F, Chan, June M, Khouri, Michel G, Douglas, Pamela S, and Eves, Neil D
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prostate Cancer, Aging, Prevention, Clinical Trials and Supportive Activities, Clinical Research, Cardiovascular, Cancer, Urologic Diseases, Blood Glucose, Body Composition, Brachial Artery, Erectile Dysfunction, Exercise Therapy, Humans, Lipids, Male, Oxygen Consumption, Prostatectomy, Prostatic Neoplasms, Regional Blood Flow, Walking, Exercise training, Prostate cancer, Efficacy, Exercise capacity, Endothelial function, Urology & Nephrology, Clinical sciences
Abstract: UnlabelledErectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n=25 per group) after RP. AT consisted of five walking sessions per week at 55-100% of peak oxygen uptake (VO2peak) for 30-60 min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow-mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤ 21) decreased by 20% in the AT group and by 24% in the UC group (difference: p=0.406). There were no significant between-group differences in any erectile function subscale (p>0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP.Trial registrationClinicaltrials.gov identifier NCT00620932.
Published: 2014

6. High detection rate of osteoporosis with screening of a general hospitalized population: a 6-year study in 6406 patients in a university hospital setting

Author: Malaise, Olivier, Detroz, Marie, Leroy, Mathieu, Leonori, Lorenzo, Seidel, Laurence, and Malaise, Michel G.
Published: 2020
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7. Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses

Author: Yoonsu Cho, Ben Michael Brumpton, Jaakko Kaprio, Johan Håkon Bjørngaard, Elliot M. Tucker-Drob, Tim T Morris, Neil M Davies, Sean Harrison, Laurence J. Howe, Wei-Min Chen, Nancy L. Pedersen, Gunnhild Åberge Vie, Kristian Hveem, Karl Heilbron, Fernando Pires Hartwig, Michel G. Nivard, Gibran Hemani, Laura D Howe, George Davey Smith, David M. Evans, Michael C. Neale, Bjørn Olav Åsvold, Eleanor Sanderson, Adam Auton, Andrew D. Grotzinger, Shuai Li, Amanda Hughes, Cristen J. Willer, Chandra A. Reynolds, Frank Windmeijer, Dorret I. Boomsma, John L. Hopper, Alexandra Havdahl, Institute for Molecular Medicine Finland, Department of Public Health, University of Helsinki, HUS Helsinki and Uusimaa Hospital District, APH - Methodology, APH - Mental Health, Biological Psychology, Brumpton, Ben [0000-0002-3058-1059], Sanderson, Eleanor [0000-0001-5188-5775], Hartwig, Fernando Pires [0000-0003-3729-0710], Harrison, Sean [0000-0002-7966-0700], Vie, Gunnhild Åberge [0000-0003-1552-5291], Cho, Yoonsu [0000-0001-6118-6652], Havdahl, Alexandra [0000-0002-9268-0423], Neale, Michael [0000-0003-4887-659X], Nivard, Michel G [0000-0003-2015-1888], Grotzinger, Andrew [0000-0001-7852-9244], Morris, Tim [0000-0001-8178-6815], Willer, Cristen [0000-0001-5645-4966], Evans, David M [0000-0003-0663-4621], Kaprio, Jaakko [0000-0002-3716-2455], Davey Smith, George [0000-0002-1407-8314], Hemani, Gibran [0000-0003-0920-1055], Davies, Neil M [0000-0002-2460-0508], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), gene-environment correlation, Epidemiology, General Physics and Astronomy, Matematikk og Naturvitenskap: 400::Basale biofag: 470 [VDP], Body Mass Index, 0302 clinical medicine, HEIGHT, Risk Factors, Genetics research, genetics, 030212 general & internal medicine, lcsh:Science, Multidisciplinary, Confounding, Mendelian Randomization Analysis, ASSOCIATION, 3142 Public health care science, environmental and occupational health, educational attainment, Female, TRAITS, TRANSMISSION, Science, Biology, Population stratification, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, BMI, 03 medical and health sciences, Medical research, SDG 3 - Good Health and Well-being, Mendelian randomization, Genetics, LINKAGE, Humans, Matematikk og Naturvitenskap: 400 [VDP], COMMON, Linkage (software), EDUCATIONAL-ATTAINMENT, Assortative mating, Gene-environment correlation, General Chemistry, confounding, BODY-MASS INDEX, 3141 Health care science, 030104 developmental biology, Matematikk og Naturvitenskap: 400::Basale biofag: 470::Genetikk og genomikk: 474 [VDP], INFERENCE, lcsh:Q, DISEQUILIBRIUM, Body mass index, height, Demography
Abstract: Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe. Both Mendelian randomization estimates using unrelated individuals and within family methods reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while Mendelian randomization estimates from samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects were strongly attenuated in within-family Mendelian randomization analyses. Our findings indicate the necessity of controlling for population structure and familial effects in Mendelian randomization studies., Family-based study designs have been applied to resolve confounding by population stratification, dynastic effects and assortative mating in genetic association analyses. Here, Brumpton et al. describe theory and simulations for overcoming such biases in Mendelian randomization through within-family studies.
Published: 2020

8. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, 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Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M 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S.G., Ruzyllo W., Gosselin G., Maggioni A.P., White H.D., Bhargava B., Min J.K., John Mancini G.B., Berman D.S., Picard M.H., Kwong R.Y., Ali Z.A., Mark D.B., Spertus J.A., Krishnan M.N., Elghamaz A., Moorthy N., Hueb W.A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T.D., Szwed H., Doerr R., Keltai M., Selvanayagam J.B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N.O., Harrell F.E., Rockhold F.W., Broderick S., Bruce Ferguson T., Williams D.O., Harrington R.A., Stone G.W., Rosenberg Y, and ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, 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Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, 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Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud 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Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020

9. The onset of preclinical Alzheimer's disease in monozygotic twins

Author: Charlotte E. Teunissen, Jori Tomassen, Elles Konijnenberg, Mara ten Kate, Pieter Jelle Visser, Michel G. Nivard, Bart N.M. van Berckel, Betty M. Tijms, Anouk den Braber, Sandra D. Mulder, Maqsood Yaqub, Dorret I. Boomsma, Adriaan A. Lammertsma, Hugo Vanderstichele, Philip Scheltens, Neurology, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Clinical chemistry, Human genetics, AMS - Tissue Function & Regeneration, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Biological Psychology, APH - Mental Health, APH - Methodology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Psychiatrie & Neuropsychologie
Subjects: 0301 basic medicine, Apolipoprotein E, Male, medicine.medical_specialty, Amyloid, Genotype, tau Proteins, Disease, Environment, Neuropsychological Tests, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Apolipoproteins E, Alzheimer Disease, Internal medicine, Medicine, Humans, Generalized estimating equation, Research Articles, Aged, Aged, 80 and over, Amyloid beta-Peptides, medicine.diagnostic_test, business.industry, Depression, Twins, Monozygotic, Middle Aged, Pathophysiology, Peptide Fragments, 030104 developmental biology, Endocrinology, Neurology, Positron emission tomography, Positron-Emission Tomography, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Research Article
Abstract: Objective The present work was undertaken to study the genetic contribution to the start of Alzheimer's disease (AD) with amyloid and tau biomarkers in cognitively intact older identical twins.Methods We studied in 96 monozygotic twin-pairs relationships between amyloid-beta (A beta) aggregation as measured by the A beta 1-42/1-40 ratio in cerebrospinal fluid (CSF; n = 126) and positron emission tomography (PET, n = 194), and CSF markers for A beta production (beta-secretase 1, A beta 1-40, and A beta 1-38) and CSF tau. Associations among markers were tested with generalized estimating equations including a random effect for twin status, adjusted for age, gender, and apolipoprotein E epsilon 4 genotype. We used twin analyses to determine relative contributions of genetic and/or environmental factors to AD pathophysiological processes.Results Twenty-seven individuals (14%) had an abnormal amyloid PET, and 14 twin-pairs (15%) showed discordant amyloid PET scans. Within twin-pairs, A beta production markers and total-tau (t-tau) levels strongly correlated (r range = 0.73-0.86, all p < 0.0001), and A beta aggregation markers and 181-phosphorylated-tau (p-tau) levels correlated moderately strongly (r range = 0.50-0.64, all p < 0.0001). Cross-twin cross-trait analysis showed that A beta 1-38 in one twin correlated with A beta 1-42/1-40 ratios, and t-tau and p-tau levels in their cotwins (r range = -0.28 to 0.58, all p < .007). Within-pair differences in A beta production markers related to differences in tau levels (r range = 0.49-0.61, all p < 0.0001). Twin discordance analyses suggest that A beta production and tau levels show coordinated increases in very early AD.Interpretation Our results suggest a substantial genetic/shared environmental background contributes to both A beta and tau increases, suggesting that modulation of environmental risk factors may aid in delaying the onset of AD pathophysiological processes. ANN NEUROL 2021
Published: 2021

10. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

Author: Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Johannesson, Magnus, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chris, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Snieder, Harold, Perry, John R. B., Ong, Ken K., den Hoed, Marcel, Barban, Nicola, Day, Felix R., Mills, M. C., Tropf, F. C., Brazel, D. M., van Zuydam, N., Vaez, A., Agbessi, M., Ahsan, H., Alves, I., Andiappan, A. K., Arindrarto, W., Awadalla, P., Battle, A., Beutner, F., Jan Bonder, M., Boomsma, D. I., Christiansen, M. W., Claringbould, A., Deelen, P., Esko, T., Fave, M. -J., Franke, L., Frayling, T., Gharib, S. A., Gibson, G., Heijmans, B. T., Hemani, G., Jansen, R., Kahonen, M., Kalnapenkis, A., Kasela, S., Kettunen, J., Kim, Y., Kirsten, H., Kovacs, P., Krohn, K., Kronberg, J., Kukushkina, V., Kutalik, Z., Lee, B., Lehtimaki, T., Loeffler, M., Marigorta, U. M., Mei, H., Milani, L., Montgomery, G. W., Muller-Nurasyid, M., Nauck, M., Nivard, M. G., Penninx, B. W. J. H., Perola, M., Pervjakova, N., Pierce, B. L., Powell, J., Prokisch, H., Psaty, B. M., Raitakari, O. T., Ripatti, S., Rotzschke, O., Rueger, S., Saha, A., Scholz, M., Schramm, K., Seppala, I., Slagboom, E. P., Stehouwer, C. D. A., Stumvoll, M., Sullivan, P., 't Hoen, P. A. C., Teumer, A., Thiery, J., Tong, L., Tonjes, A., van Dongen, J., van Iterson, M., van Meurs, J., Veldink, J. H., Verlouw, J., Visscher, P. M., Volker, U., Vosa, U., Westra, H. -J., Wijmenga, C., Yaghootkar, H., Yang, J., Zeng, B., Zhang, F., van Greevenbroek, M. M. J., Schalkwijk, C. G., Deelen, J., van Heemst, D., van Duijn, C. M., Hofman, B. A., Isaacs, A., Uitterlinden, A. G., Verbiest, M., Suchiman, H. E. D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Bot, J., Zhernakova, D. V., Luijk, R., Bonder, M. J., Swertz, M. A., van Zwet, E. W., Akimova, E. T., Bergmann, S., Boardman, J. D., Buring, J. E., Cesarini, D., Chasman, D. I., Chavarro, J. E., Cocca, M., Concas, M. P., Davey-Smith, G., Davies, G., Deary, I. J., Gaskins, A. J., de Geus, E. J. C., Gieger, C., Girotto, G., Grabe, H. J., Gunderson, E. P., Harris, K. M., Hartwig, F. P., He, C., Homuth, G., Horta, B. L., Jan Hottenga, J., Huang, H., Hyppӧnen, E., Ikram, M. A., Johannesson, M., Kamali, Z., Kavousi, M., Kraft, P., Kuhnel, B., Langenberg, C., Study, L. C., Lind, P. A., Luan, J., Magi, R., Magnusson, P. K. E., Mahajan, A., Martin, N. G., Mbarek, H., Mccarthy, M. I., Mcmahon, G., Mcqueen, M. B., Medland, S. E., Meitinger, T., Metspalu, A., Mihailov, E., Missmer, S. A., Mollegaard, S., Mook-Kanamori, D. O., Morgan, A., van der Most, P. J., de Mutsert, R., Noordam, R., Power, C., Redmond, P., Rich-Edwards, J. W., Ridker, P. M., Rietveld, C. A., Ring, S. M., Rose, L. M., Rueedi, R., Stefansson, K., Stockl, D., Strauch, K., Thurik, A. R., Timpson, N. J., Turman, C., Wareham, N. J., Willemsen, G., Zhao, J. H., Pers, T. H., Snieder, H., Perry, J. R. B., Ong, K. K., den Hoed, M., Barban, N., Day, F. R., Mills, Melinda C, Tropf, Felix C, Brazel, David M, van Zuydam, Natalie, Vaez, Ahmad, Pers, Tune H, Snieder, Harold, Perry, John RB, Ong, Ken K, den Hoed, Marcel, Barban, Nicola, Day, Felix R, Hyppӧnen, Elina, eQTLGen Consortium, BIOS Consortium, Human Reproductive Behaviour Consortium, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Consortium, eQTLGen, Consortium, BIOS, Consortium, Human Reproductive Behaviour, Mahajan, A, McCarthy, MI, Mills, Melinda C., Tropf, Felix C., Brazel, David M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Marku, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Jori, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthij, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Ikram, M. Arfan, Johannesson, Magnu, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thoma, Metspalu, Andre, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chri, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Dori, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Perry, John R. B., Ong, Ken K., Day, Felix R., Sociology [until 2010], Biological Psychology, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Management and Organisation, Urology, Medical Informatics, Department of Marketing Management, Epidemiology, Internal Medicine, Radiology & Nuclear Medicine, Neurology, Applied Economics, and Life Course Epidemiology (LCE)
Subjects: Male, demography, genetic variants, reproductive biology, externalising behavior, environmental effects, Disease, Genome-wide association studies, Behavioral Neuroscience, 0302 clinical medicine, genetics, media_common, fertility, 0303 health sciences, Reproduction, Incidence (epidemiology), Coitus, Age Factors, Longevity, sexual intercourse, health, Spermatid differentiation, Single Nucleotide, Reproduction/genetics, 3. Good health, Behavioural genetics, Parturition/genetics, Female, infertility, Infertility, genetic variant, Adolescent, Social Psychology, media_common.quotation_subject, Experimental and Cognitive Psychology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Reproductive biology, medicine, Humans, Polymorphism, behavioural genetics, first sexual intercourse, Genetic Association Studies, Demography, 030304 developmental biology, Parturition, Coitus/physiology, medicine.disease, externalising behaviour, Sexual intercourse, Fertility, age, 030217 neurology & neurosurgery, first birth
Abstract: Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.
Published: 2021

11. Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease in Patients With a History of Heart Failure or Left Ventricular Dysfunction

Author: Susanna R. Stevens, Ariel Diaz, Ileana L. Piña, Aldo P. Maggioni, David J. Maron, Jose Lopez-Sendon, Joseph B. Selvanayagam, Mark A de Belder, Michel G. Khouri, Denis Phaneuf, Ahmed Elghamaz, Yi-tong Ma, Frank W. Rockhold, Derek J. Hausenloy, Luis A. Guzman, Gregg W. Stone, Renato D. Lopes, Alessandro Sionis, Judith S. Hochman, Alexander Chernyavskiy, Pedro Silvio Farsky, Rolf Doerr, Karen P. Alexander, and Harmony R. Reynolds
Subjects: Male, medicine.medical_specialty, Invasive strategy, Conservative management, medicine.medical_treatment, Myocardial Infarction, Ischemia, heart failure, Disease, Disease-Free Survival, Article, Ventricular Dysfunction, Left, Risk Factors, left, Physiology (medical), Internal medicine, medicine, Humans, In patient, Aged, Heart Failure, business.industry, percutaneous coronary intervention, Percutaneous coronary intervention, ventricular dysfunction, Middle Aged, medicine.disease, Survival Rate, myocardial ischemia, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, Ischemic heart, business, Follow-Up Studies
Abstract: Background: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but Methods: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years. Results: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, −12.1% [95% CI, −22.6 to −1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, −1.6% [95% CI, −3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy–associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF. Conclusions: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522.
Published: 2020

12. A randomized controlled trial comparing changes in fitness with or without supervised exercise in patients initiated on enzalutamide and androgen deprivation therapy for non-metastatic castration-sensitive prostate cancer (EXTEND)

Author: Michael R. Harrison, Paul G. Davis, Michel G. Khouri, David B. Bartlett, Rajan T. Gupta, Andrew J. Armstrong, Megan A. McNamara, Tian Zhang, Monika Anand, Kelly Onyenwoke, Sara Edwardson, Danielle Craig, Meghan Michalski, Yuan Wu, Taofik Oyekunle, Brian Coyne, Aubrie Coburn, Lee W. Jones, and Daniel J. George
Subjects: Male, Cancer Research, Urology, Prostatic Neoplasms, Androgen Antagonists, Article, Exercise Therapy, Oncology, Benzamides, Nitriles, Phenylthiohydantoin, Androgens, Quality of Life, Humans, Neoplasm Recurrence, Local, Orchiectomy
Abstract: BACKGROUND: Androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSI) are associated with deleterious physical effects, which exercise may mitigate; however, exercise has never been studied in patients initiating treatment with ADT and an ARSI. Our objective was to determine whether supervised exercise prior to and during initial therapy could mitigate adverse effects of ADT plus enzalutamide. METHODS: We conducted a single center trial in patients with recurrent prostate cancer treated with ADT and enzalutamide. We randomized 26 patients to 16 weeks of supervised exercise (aerobic and resistance), starting 4 weeks before initiation of ADT and enzalutamide, or usual care. The primary endpoint was change in peak oxygen uptake (VO(2)peak) as a measure of cardiorespiratory fitness (CRF). Secondary endpoints were functional capacity, maximal strength, body composition, patient-reported outcomes, safety, and feasibility. Analysis of covariance was used to compare outcomes for groups at Week 17 adjusted for baseline values. RESULTS: The usual care group (N=13) showed declines from baseline to week 17 in both absolute CRF (−0.31 L/min, −10.9%; p
Published: 2022

13. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Gabriëlla A.M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, Robert Handa, David St Clair, Todd Lencz, Bryan J. Mowry, Sathish Periyasamy, Murray J. Cairns, Paul A. Tooney, Jing Qin Wu, Brian Kelly, George Kirov, Patrick F. Sullivan, Aiden Corvin, Brien P. Riley, Tõnu Esko, Lili Milani, Erik G. Jönsson, Aarno Palotie, Hannelore Ehrenreich, Martin Begemann, Agnes Steixner-Kumar, Pak C. Sham, Nakao Iwata, Daniel R. Weinberger, Pablo V. Gejman, Alan R. Sanders, Joseph D. Buxbaum, Dan Rujescu, Ina Giegling, Bettina Konte, Annette M. Hartmann, Elvira Bramon, Robin M. Murray, Michele T. Pato, Jimmy Lee, Ingrid Melle, Espen Molden, Roel A. Ophoff, Andrew McQuillin, Nicholas J. Bass, Rolf Adolfsson, Anil K. Malhotra, Nicholas G. Martin, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Andreas J. Forstner, Franziska Degenhardt, Sabrina Schaupp, Ashley L. Comes, Manolis Kogevinas, José Guzman-Parra, Andreas Reif, Fabian Streit, Lea Sirignano, Sven Cichon, Maria Grigoroiu-Serbanescu, Joanna Hauser, Jolanta Lissowska, Fermin Mayoral, Bertram Müller-Myhsok, Beata Świątkowska, Thomas G. Schulze, Markus M. Nöthen, Marcella Rietschel, John Kelsoe, Marion Leboyer, Stéphane Jamain, Bruno Etain, Frank Bellivier, John B. Vincent, Martin Alda, Claire O’Donovan, Pablo Cervantes, Joanna M. Biernacka, Mark Frye, Susan L. McElroy, Laura J. Scott, Eli A. Stahl, Mikael Landén, Marian L. Hamshere, Olav B. Smeland, Srdjan Djurovic, Arne E. Vaaler, Ole A. Andreassen, Bernhard T. Baune, Tracy Air, Martin Preisig, Rudolf Uher, Douglas F. Levinson, Myrna M. Weissman, James B. Potash, Jianxin Shi, James A. Knowles, Roy H. Perlis, Susanne Lucae, Dorret I. Boomsma, Brenda W.J.H. Penninx, Jouke-Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Yuri Milaneschi, Henning Tiemeier, Hans J. Grabe, Alexander Teumer, Sandra Van der Auwera, Uwe Völker, Steven P. Hamilton, Patrik K.E. Magnusson, Alexander Viktorin, Divya Mehta, Niamh Mullins, Mark J. Adams, Gerome Breen, Andrew M. McIntosh, Cathryn M. Lewis, David M. Hougaard, Merete Nordentoft, Ole Mors, Preben B. Mortensen, Thomas Werge, Thomas D. Als, Anders D. Børglum, Tracey L. Petryshen, Jordan W. Smoller, Jill M. Goldstein, Stephan Ripke, Benjamin M. Neale, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee Chee Keong, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Sandra Meier, Carin J. Meijer, Bela Melegh, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Vihra Milanova, Younes Mokrab, Derek W. Morris, Kieran C. Murphy, Inez Myin-Germeys, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Ulrich Schall, Christian R. Schubert, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Douglas H.R. Blackwood, Ariel Darvasi, Enrico Domenici, Michael Gill, Hugh Gurling, Christina M. Hultman, Assen V. Jablensky, Kenneth S. Kendler, Jo Knight, Qingqin S. Li, Jianjun Liu, Steven A. McCarroll, Jennifer L. Moran, Michael J. Owen, Carlos N. Pato, Danielle Posthuma, Pamela Sklar, Jens R. Wendland, Mark J. Daly, Michael C. O’Donovan, Peter Donnelly, Ines Barroso, Jenefer M. Blackwell, Matthew A. Brown, Juan P. Casas, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Gavin Band, Céline Bellenguez, Colin Freeman, Eleni Giannoulatou, Garrett Hellenthal, Richard Pearson, Matti Pirinen, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Sarah Edkins, Matthew Gillman, Emma Gray, Rhian Gwilliam, Naomi Hammond, Sarah E. Hunt, Alagurevathi Jayakumar, Jennifer Liddle, Owen T. McCann, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Avazeh Tashakkori-Ghanbaria, Matthew Waller, Paul Weston, Pamela Whittaker, Sara Widaa, Mark I. McCarthy, Maria J. Arranz, Steven Bakker, Stephan Bender, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Stephen Lawrie, Kuang Lin, Don H. Linszen, Ignacio Mata, Muriel Walshe, Matthias Weisbrod, Durk Wiersma, Vassily Trubetskoy, Yunpeng Wang, Jonathan R.I. Coleman, Héléna A. Gaspar, Christiaan A. de Leeuw, Jennifer M. Whitehead Pavlides, Maciej Trzaskowski, Enda M. Byrne, Liam Abbott, Huda Akil, Diego Albani, Ney Alliey-Rodriguez, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A. Badner, Marie Bækvad-Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Richard Belliveau, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Jonas Bybjerg-Grauholm, Miquel Casas, Felecia Cerrato, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, Claire Churchhouse, Toni-Kim Clarke, William Coryell, David W. Craig, Cristiana Cruceanu, Piotr M. Czerski, Anders M. Dale, Simone de Jong, Jurgen Del-Favero, J. Raymond DePaulo, Amanda L. Dobbyn, Ashley Dumont, Torbjørn Elvsåshagen, Chun Chieh Fan, Sascha B. Fischer, Matthew Flickinger, Tatiana M. Foroud, Liz Forty, Christine Fraser, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Marianne Giørtz Pedersen, Jaqueline Goldstein, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Melissa J. Green, Tiffany A. Greenwood, Weihua Guan, Martin Hautzinger, Urs Heilbronner, Maria Hipolito, Dominic Holland, Laura Huckins, Jessica S. Johnson, Radhika Kandaswamy, Robert Karlsson, Sarah Kittel-Schneider, Anna C. Koller, Ralph Kupka, Catharina Lavebratt, Jacob Lawrence, William B. Lawson, Markus Leber, Phil H. Lee, Shawn E. Levy, Jun Z. Li, Chunyu Liu, Anna Maaser, Donald J. MacIntyre, Pamela B. Mahon, Lina Martinsson, Steve McCarroll, Peter McGuffin, Melvin G. McInnis, James D. McKay, Helena Medeiros, Sarah E. Medland, Fan Meng, Grant W. Montgomery, Thomas W. Mühleisen, Hoang Nguyen, Caroline M. Nievergelt, Annelie Nordin Adolfsson, Evaristus A. Nwulia, Claire O'Donovan, Loes M. Olde Loohuis, Anil P.S. Ori, Lilijana Oruc, Urban Ösby, Amy Perry, Andrea Pfennig, Eline J. Regeer, Céline S. Reinbold, John P. Rice, Fabio Rivas, Margarita Rivera, Euijung Ryu, Cristina Sánchez-Mora, Alan F. Schatzberg, William A. Scheftner, Nicholas J. Schork, Cynthia Shannon Weickert, Tatyana Shehktman, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Christine Søholm Hansen, Anne T. Spijker, Michael Steffens, John S. Strauss, Szabolcs Szelinger, Robert C. Thompson, Thorgeir E. Thorgeirsson, Jens Treutlein, Helmut Vedder, Weiqing Wang, Stanley J. Watson, Thomas W. Weickert, Simon Xi, Wei Xu, Allan H. Young, Peter Zandi, Peng Zhang, Sebastian Zöllner, Abdel Abdellaoui, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Fernando S. Goes, Lynsey S. Hall, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Christel M. Middeldorp, Evelin Mihailov, Francis M. Mondimore, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O'Reilly, Hogni Oskarsson, Jodie N. Painter, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Katherine E. Tansey, Henning Teismann, Wesley Thompson, Pippa A. Thomson, Matthew Traylor, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Shantel Marie Weinsheimer, Jürgen Wellmann, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Klaus Berger, Udo Dannlowski, Katharina Domschke, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Pamela AF. Madden, Patrik K. Magnusson, Preben Bo Mortensen, Michael C. O'Donovan, Sara A. Paciga, Nancy L. Pedersen, David J. Porteous, Catherine Schaefer, Henry Völzke, Marco Bortolato, Janita Bralten, Cynthia M. Bulik, Christie L. Burton, Caitlin E. Carey, Lea K. Davis, Laramie E. Duncan, Howard J. Edenberg, Lauren Erdman, Stephen V. Faraone, Slavina B. Goleva, Wei Guo, Christopher Hübel, Laura M. Huckins, Ekaterina A. Khramtsova, Joanna Martin, Carol A. Mathews, Elise Robinson, Eli Stahl, Barbara E. Stranger, Michela Traglia, Raymond K. Walters, Lauren A. Weiss, Stacey J. Winham, Yin Yao, Kristjar Skajaa, Markus Nöthen, Michael Owen, Robert H. Yolken, Niels Plath, Jonathan Mill, Daniel Geschwind, Psychiatry 1, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Functional Genomics, Biological Psychology, APH - Mental Health, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Blokland, Gabriella AM, Grove, Jakob, Chen, Chia Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Lee, Sang Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, iPSYCH, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Male, Bipolar Disorder, Schizophrenia/genetics, LD SCORE REGRESSION, Genome-wide association study, 0302 clinical medicine, Receptors, SCHIZOPHRENIA, Psychotic Disorders/genetics, KYNURENINE PATHWAY METABOLISM, Genetics, RISK, Sex Characteristics, Vascular Endothelial Growth Factor, Bipolar Disorder/genetics, Major/genetics, Single Nucleotide, AFFECTIVE STIMULI IMPACT, Schizophrenia, Sulfurtransferases, Major depressive disorder, Female, Depressive Disorder, Major/genetics, Bipolar disorder, Locus (genetics), Genomics, Biology, Polymorphism, Single Nucleotide, Article, DYSPHORIC MOOD, 03 medical and health sciences, Sex differences, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Polymorphism, GENOME-WIDE ASSOCIATION, Genotype-by-sex interaction, Biological Psychiatry, Depressive Disorder, Major, Depressive Disorder, GENDER-DIFFERENCES, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], PARAVENTRICULAR NUCLEUS, 3112 Neurosciences, Endothelial Cells, MAJOR DEPRESSION, medicine.disease, Genetic architecture, 030104 developmental biology, Mood, Receptors, Vascular Endothelial Growth Factor, Psychotic Disorders, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
Published: 2022

14. Identification of Undetected Monogenic Cardiovascular Disorders

Author: Fawaz Alenezi, Lauren K. Truby, Lydia Coulter Kwee, Aris Baras, Michel G. Khouri, Andrew Wang, Christopher L. Holley, James P. Daubert, Albert Y. Sun, Robert W. McGarrah, Sreekanth Vemulapalli, Svati H. Shah, Jawan W. Abdulrahim, Teminioluwa A. Ajayi, and Ricardo Henao
Subjects: Male, medicine.medical_specialty, Familial hypercholesterolemia, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Exome Sequencing, Prevalence, medicine, Electronic Health Records, Humans, Genetic Testing, 030212 general & internal medicine, Medical diagnosis, Hemochromatosis Protein, Exome sequencing, Sequence Deletion, Genetic testing, Missed Diagnosis, medicine.diagnostic_test, business.industry, Amyloidosis, alpha-Glucosidases, Middle Aged, medicine.disease, United States, Cardiovascular Diseases, Clinical diagnosis, Genomic Structural Variation, Cohort, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Background Monogenic diseases are individually rare but collectively common, and are likely underdiagnosed. Objectives The purpose of this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentially missed diagnoses in a cardiovascular cohort. Methods Exomes from 8,574 individuals referred for cardiac catheterization were analyzed. Pathogenic/likely pathogenic (P/LP) variants associated with MCVD (cardiomyopathies, arrhythmias, connective tissue disorders, and familial hypercholesterolemia were identified. Electronic health records (EHRs) were reviewed for individuals harboring P/LP variants who were predicted to develop disease (G+). G+ individuals who did not have a documented relevant diagnosis were classified into groups of whether they may represent missed diagnoses (unknown, unlikely, possible, probable, or definite) based on relevant diagnostic criteria/features for that disease. Results In total, 159 P/LP variants were identified; 2,361 individuals harbored at least 1 P/LP variant, of whom 389 G+ individuals (4.5% of total cohort) were predicted to have at least 1 MCVD. EHR review of 342 G+ individuals predicted to have 1 MCVD with sufficient EHR data revealed that 52 had been given the relevant clinical diagnosis. The remaining 290 individuals were classified as potentially having an MCVD as follows: 193 unlikely (66.6%), 50 possible (17.2%), 30 probable (10.3%), and 17 definite (5.9%). Grouping possible, probable, definite, and known diagnoses, 149 were considered to have an MCVD. Novel MCVD pathogenic variants were identified in 16 individuals. Conclusions Overall, 149 individuals (1.7% of cohort) had MCVDs, but only 35% were diagnosed. These patients represents a “missed opportunity,” which could be addressed by greater use of genetic testing of patients seen by cardiologists.
Published: 2020

15. Outcomes following cardioversion for patients with cardiac amyloidosis and atrial fibrillation or atrial flutter

Author: Sean D. Pokorney, Eric Black-Maier, Kyle R. Geurink, Michael Rehorn, Amanda C. Coniglio, Michel G. Khouri, and Rahul S. Loungani
Subjects: Male, Bradycardia, medicine.medical_specialty, Biopsy, medicine.medical_treatment, Electric Countershock, Magnetic Resonance Imaging, Cine, 030204 cardiovascular system & hematology, Cardioversion, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cause of Death, Internal medicine, Atrial Fibrillation, medicine, Humans, Sinus rhythm, cardiovascular diseases, 030212 general & internal medicine, Aged, Retrospective Studies, business.industry, Myocardium, Amyloidosis, Atrial fibrillation, Retrospective cohort study, Prognosis, medicine.disease, United States, Survival Rate, Atrial Flutter, Cardiac amyloidosis, cardiovascular system, Cardiology, Female, Morbidity, medicine.symptom, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business, Atrial flutter, Follow-Up Studies
Abstract: Atrial arrhythmias commonly occur in patients with cardiac amyloidosis (CA), but there is limited data on safety or efficacy of cardioversion (DCCV) for management of these rhythms in CA. We identified 25 patients with CA (20 with transthyretin (TTR) and 5 with light-chain (AL) amyloidosis) at Duke University who underwent DCCV for atrial arrhythmias and documented procedural success, complications, and long-term morbidity and mortality. While DCCV successfully restored sinus rhythm in 96% of patients, 36% of patients experienced immediate procedural complications (primarily bradycardia and hypotension), 80% had recurrence of atrial arrhythmias at 1 year, and 52% died at 3 years, highlighting short-term safety concerns, long-term inefficacy, and poor prognosis associated with symptomatic atrial arrhythmias requiring DCCV in CA.
Published: 2020

16. A Case of Infected Left Atrial Myxoma Presenting as ST-Elevation Myocardial Infarction (STEMI)

Author: Matthew Peters, Michel G. Farah, and Khaled W. Tuwairqi
Subjects: Adult, Male, medicine.medical_specialty, Acute coronary syndrome, medicine.medical_treatment, 030204 cardiovascular system & hematology, Transesophageal echocardiogram, Coronary Angiography, Diagnosis, Differential, Heart Neoplasms, Electrocardiography, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Streptococcal Infections, Internal medicine, Mitral valve, Humans, Medicine, cardiovascular diseases, Myocardial infarction, Acute Coronary Syndrome, Cardiac Surgical Procedures, medicine.diagnostic_test, business.industry, Coronary Thrombosis, Ceftriaxone, Mitral valve replacement, Streptococcus, Myxoma, Articles, General Medicine, medicine.disease, Anti-Bacterial Agents, medicine.anatomical_structure, 030220 oncology & carcinogenesis, cardiovascular system, Cardiology, ST Elevation Myocardial Infarction, Gentamicins, Left Atrial Myxoma, business, Echocardiography, Transesophageal
Abstract: Patient: Male, 34-year-old Final Diagnosis: Infected atrial myxoma Symptoms: Chest pain Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Rare disease Background: Although left atrial myxoma is the most common benign primary cardiac tumor, infected atrial myxoma is rare. This report presents a case of infected left atrial myxoma with embolization to the left anterior descending (LAD) coronary artery, which was identified following an initial presentation with ST-elevation myocardial infarction (STEMI). Case Report: A 34-year-old man with a history of smoking tobacco and intravenous cocaine use presented to the emergency room with symptoms of a feeling of pressure on the chest and symptoms in the left arm. An electrocardiogram (ECG) showed ST elevation in leads II, III, aVF, and V3–V5, consistent with an anterior-inferior STEMI. He underwent percutaneous intervention (PCI) with two drug-eluting stents to the mid-distal LAD coronary artery. The patient also had fever, chills, a history of weight loss, and signs of peripheral emboli. Blood cultures identified Gram-positive Streptococcus parasanguinis, a member of the Streptococcus viridans group. Transesophageal echocardiogram (TEE) identified a large, mobile, pedunculated left atrial mass protruding into the mitral valve in diastole and mitral valve vegetations. Surgical excision and the histology confirmed a diagnosis of benign left atrial myxoma containing Gram-positive cocci. The patient required mitral valve replacement and a postoperative two-week course of gentamicin and a six-week course of ceftriaxone Conclusions: A rare case is reported of infected left atrial myxoma presenting as STEMI secondary to coronary artery embolization, which was treated with PCI, antibiotics, and mitral valve replacement.
Published: 2019

17. Estimating direct and indirect genetic effects on offspring phenotypes using genome-wide summary results data

Author: Liang-Dar Hwang, Michel G. Nivard, Nicole M. Warrington, David M. Evans, and Biological Psychology
Subjects: Adult, Male, Multivariate statistics, Genotype, Population genetics, Science, media_common.quotation_subject, Inheritance Patterns, General Physics and Astronomy, Fertility, Genome-wide association study, Computational biology, Biology, Quantitative trait locus, Quantitative trait, Genome-wide association studies, Article, General Biochemistry, Genetics and Molecular Biology, Structural equation modeling, Risk-Taking, Humans, Autistic Disorder, Genetic Association Studies, Biological Specimen Banks, media_common, Genetic association, Multidisciplinary, Models, Genetic, Genome, Human, Siblings, Infant, Genomics, General Chemistry, Biobank, United Kingdom, Phenotype, Genetic Loci, Latent Class Analysis, Educational Status, Female, Genome-Wide Association Study
Abstract: Estimation of direct and indirect (i.e. parental and/or sibling) genetic effects on phenotypes is becoming increasingly important. We compare several multivariate methods that utilize summary results statistics from genome-wide association studies to determine how well they estimate direct and indirect genetic effects. Using data from the UK Biobank, we contrast point estimates and standard errors at individual loci compared to those obtained using individual level data. We show that Genomic structural equation modelling (SEM) outperforms the other methods in accurately estimating conditional genetic effects and their standard errors. We apply Genomic SEM to fertility data in the UK Biobank and partition the genetic effect into female and male fertility and a sibling specific effect. We identify a novel locus for fertility and genetic correlations between fertility and educational attainment, risk taking behaviour, autism and subjective well-being. We recommend Genomic SEM be used to partition genetic effects into direct and indirect components when using summary results from genome-wide association studies., Estimating direct and indirect effects of genotypes on phenotypes is important for genetic analyses such as Mendelian randomization. Here the authors compare five different methods to estimate direct and indirect genetic effects using summary results statistics that account for sample overlap.
Published: 2021

18. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Author: Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J. van, Taskesen, Erdogan, Yang, Wu, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Metspalu, Andres, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bram t, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J. van der, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J. van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Mcmahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johannes, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Duijn, Cornelia M. van, Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Harst, Pim van der, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Johannesson, Magnus, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Urs, Harris, Kathleen Mullan, Hasler, Gregor, Ikram, Mohammad A., Jain, Sonia, Kessler, Ronald C., Kooyman, Maarten, Mackillop, James, Männikkö, Minna, Morcillo-Suarez, Carlos, Mcqueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthias, White, Jon, Wit, Harriet de, Fehr, Ernst, Kumari, Meena, Laibson, David, Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Adult Psychiatry, APH - Mental Health, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, 23and Me Research Team, eQTLgen Consortium, International Cannabis Consortium, Economics, Biological Psychology, Complex Trait Genetics, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Tinbergen Institute, 23andme Research Team, Psychiatric Genomics Consortium, Social Science Genetic Association Consortium, Linner Richard Karlsson, Biroli P, Kong Edward, Meddens Fleur W., Wedow Robbee, Fontana Mark Alan, Lebreton Mael, Tino Stephen P., Abdellaoui Abdel, Hammerschlag Anke R., Nivard Michel G., Okbay Aysu, Rietveld Cornelius A., Timshel Pascal N., Trzaskowski Maciej, de Vlaming Ronald, Zund Christian L., Bao Yanchun, Buzdugan Laura, Caplin Ann H., Chen Chia-Yen, Eibich Peter, Fontanillas Pierre, Gonzalez Juan R., Joshi Peter K., Karhunen Ville, Kleinman Aaron, Levin Remy Z., Lill Christina M., Meddens Gerardus A., Muntane Gerard, Sanchez-Roige Sandra, van Rooij Frank J., Taskesen Erdogan, Wu Yang, Zhang Futao, Agee Michelle, Alipanahi Babak, Bell Robert K., Bryc Katarzyna, Elson Sarah L., Furlotte Nicholas A., Huber Karen E., Litterman Nadia K., McCreight Jennifer C., McIntyre Matthew H., Mountain Joanna L., Northover Carrie A. M., Pitts Steven J., Sathirapongsasuti J. Fah, Sazonova Olga V., Shelton Janie F., Shringarpure Suyash, Tian Chao, Tung Joyce Y., Vacic Vladimir, Wilson Catherine H., Agbessi Mawusse, Ahsan Habibul, Alves Isabel, Andiappan Anand, Awadalla Philip, Battle Alexi, Beutner Frank, Bonder Marc Jan, Boomsma Dorret I., Christiansen Mark, Claringbould Annique, Deelen Patrick, Esko Tonu, Fave Marie-Julie, Franke Lude, Frayling Timothy, Gharib Sina A., Gibson Gregory, Heijmans Bastiaan, Hemani Gibran, Jansen Rick, Kahonen Mika, Kalnapenkis Anette, Kasela Silva, Kettunen Johanne, Kim Yungil, Kirsten Holger, Kovacs Peter, Krohn Knut, Kronberg-Guzman Jaanika, Kukushkina Viktorija, Kutalik Zoltan, Lee Bernett, Lehtimaki Terho, Loeffler Marku, Marigorta Urko M., Metspalu Andre, Milani Lili, Montgomery Grant W., Mueller-Nurasyid Martina, Nauck Matthia, Penninx Brenda, Perola Marku, Pervjakova Natalia, Pierce Brandon, Powell Joseph, Prokisch Holger, Psaty Bruce M., Raitakari Olli, Ring Susan, Ripatti Samuli, Rotzchke Olaf, Rueger Sina, Saha Ashi, Scholz Marku, Schramm Katharina, Seppala Ilkka, Stumvoll Michael, Sullivan Patrick, Hoen Peter-Bramt, Teumer Alexander, Thiery Joachim, Tong Lin, Tonjes Anke, van Dongen Jenny, van Meurs Joyce, Verlouw Joost, Visscher Peter M., Voelker Uwe, Vosa Urmo, Westra Harm-Jan, Yaghootkar Hanieh, Yang Jian, Zeng Biao, Lee James J., Pers Tune H., Turley Patrick, Chen Guo-Bo, Emilsson Valur, Oskarsson Sven, Pickrell Joseph K., Thom Kevin, Timshel Pascal, Ahluwalia Tarunveer S., Bacelis Jona, Baumbach Clemen, Bjornsdottir Gyda, Brandsma Johannes H., Concas Maria Pina, Derringer Jaime, Galesloot Tessel E., Girotto Giorgia, Gupta Richa, Hall Leanne M., Harris Sarah E., Hofer Edith, Horikoshi Momoko, Huffman Jennifer E., Kaasik Kadri, Kalafati Ioanna P., Kong Augustine, Lahti Jari, van der Lee Sven J., de Leeuw Christiaan, Lind Penelope A., Lindgren Karl-Oskar, Liu Tian, Mangino Massimo, Marten Jonathan, Mihailov Evelin, Miller Michael B., van der Most Peter J., Oldmeadow Christopher, Payton Antony, Peyrot Wouter J., Qian Yong, Rueedi Rico, Salvi Erika, Schmidt Boerge, Schraut Katharina E., Shi Jianxin, Smith Albert V., Poot Raymond A., St Pourcain Beate, Thorleifsson Gudmar, Verweij Niek, Vuckovic Dragana, Wellmann Juergen, Yang Jingyun, Zhao Wei, Zhu Zhihong, Alizadeh Behrooz Z., Amin Najaf, Bakshi Andrew, Baumeister Sebastian E., Biino Ginevra, Bonnelykke Klau, Boyle Patricia A., Campbell Harry, Cappuccio Francesco P., Davies Gail, De Neve Jan-Emmanuel, Deloukas Pano, Demuth Ilja, Ding Jun, Eisele Lewin, Eklund Niina, Evans David M., Faul Jessica D., Feitosa Mary F., Forstner Andreas J., Gandin Ilaria, Gunnarsson Bjarni, Halldorsson Bjarni V., Harris Tamara B., Heath Andrew C., Hocking Lynne J., Holliday Elizabeth G., Homuth Georg, Horan Michael A., Hottenga Jouke-Jan, de Jager Philip L., Jugessur Astanand, Kaakinen Marika A., Kanoni Stavroula, Keltigangas-Jarvinen Liisa, Kiemeney Lambertus A. L. M., Kolcic Ivana, Koskinen Seppo, Kraja Aldi T., Kroh Martin, Latvala Antti, Launer Lenore J., Lebreton Mael P., Levinson Douglas F., Lichtenstein Paul, Lichtner Peter, Liewald David C. M., Loukola Anu, Madden Pamela A., Magi Reedik, Maki-Opas Tomi, Marioni Riccardo E., Marques-Vidal Pedro, McMahon George, Meisinger Christa, Meitinger Thoma, Milaneschi Yusplitri, Myhre Ronny, Nelson Christopher P., Nyholt Dale R., Ollier William E. R., Palotie Aarno, Paternoster Lavinia, Pedersen Nancy L., Petrovic Katja E., Porteous David J., Raikkonen Katri, Ring Susan M., Robino Antonietta, Rostapshova Olga, Rudan Igor, Rustichini Aldo, Salomaa Veikko, Sanders Alan R., Sarin Antti-Pekka, Schmidt Helena, Scott Rodney J., Smith Blair H., Smith Jennifer A., Staessen Jan A., Steinhagen-Thiessen Elisabeth, Strauch Konstantin, Terracciano Antonio, Tobin Martin D., Ulivi Sheila, Vaccargiu Simona, Quaye Lydia, Venturini Cristina, Vinkhuyzen Anna A. E., Voelzke Henry, Vonk Judith M., Vozzi Diego, Waage Johanne, Ware Erin B., Willemsen Gonneke, Attia John R., Bennett David A., Berger Klau, Bertram Lar, Bisgaard Han, Borecki Ingrid B., Bultmann Ute, Chabris Christopher F., Cucca Francesco, Cusi Daniele, Deary J., Dedoussis George V., van Duijn Cornelia M., Eriksson Johan G., Franke Barbara, Gasparini Paolo, Gejman Pablo V., Gieger Christian, Grabe Hans-Joergen, Gratten Jacob, Gudnason Vilmundur, van der Harst Pim, Hayward Caroline, Hinds David A., Hoffmann Wolfgang, Hypponen Elina, Iacono William G., Jacobsson Bo, Jarvelin Marjo-Riitta, Jockel Karl-Heinz, Kaprio Jaakko, Kardia Sharon L. R., Lehrer Steven F., Magnusson Patrik K. E., Martin Nicholas G., McGue Matt, Pendleton Neil, Pirastu Nicola, Pirastu Mario, Polasek Ozren, Posthuma Danielle, Power Christine, Province Michael A., Samani Nilesh J., Schlessinger David, Schmidt Reinhold, Sorensen Thorkild I. A., Spector Tim D., Stefansson Kari, Thorsteinsdottir Unnur, Thurik A. Roy, Timpson Nicholas J., Tiemeier Henning, Uitterlinden Andre G., Vitart Veronique, Vollenweider Peter, Weir David R., Wilson James F., Wright Alan F., Conley Dalton C., Krueger Robert F., Smith George Davey, Laibson David I., Medland Sarah E., Johannesson Magnu, Koellinger Philipp D., Cesarini David, Benjamin Daniel J., Auton Adam, Boardman Jason D., Clark David W., Conlin Andrew, Dolan Conor C., Fischbacher Ur, Groenen Patrick J. F., Harris Kathleen Mullan, Hasler Gregor, Hofman Albert, Ikram Mohammad A., Jain Sonia, Karlsson Robert, Kessler Ronald C., Kooyman Maarten, MacKillop Jame, Mannikko Minna, Morcillo-Suarez Carlo, McQueen Matthew B., Schmidt Klaus M., Smart Melissa C., Sutter Matthia, White Jon, de Wit Harriet, Fehr Ernst, Kumari Meena, Laibson David, Meyer Michelle N., Navarro Arcadi, Palmer Abraham A., Schunk Daniel, Stein Murray B., Svento Rauli, Timmers Paul R. H. J., Ursano Robert J., Wagner Gert G., Beauchamp Jonathan P., Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J. van, Taskesen, Erdogan, Wu, Yang, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Metspalu, Andre, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Penninx, Brenda, Perola, Marku, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bram t, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Ahluwalia, Tarunveer S., Bacelis, Jona, Baumbach, Clemen, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J. van der, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J. van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klau, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Pano, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Mcmahon, George, Meisinger, Christa, Meitinger, Thoma, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johanne, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klau, Bertram, Lar, Bisgaard, Han, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Duijn, Cornelia M. van, Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Harst, Pim van der, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Johannesson, Magnu, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Ur, Harris, Kathleen Mullan, Hasler, Gregor, Ikram, Mohammad A., Jain, Sonia, Kessler, Ronald C., Kooyman, Maarten, Mackillop, Jame, Männikkö, Minna, Morcillo-Suarez, Carlo, Mcqueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthia, White, Jon, Wit, Harriet de, Fehr, Ernst, Kumari, Meena, Laibson, David, Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Applied Economics, Hematology, Epidemiology, Urology, Department of Marketing Management, Internal Medicine, Medical Informatics, Cell biology, Erasmus MC other, Molecular Genetics, Econometrics, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, RS: Carim - V02 Hypertension and target organ damage, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Linnér, Richard Karlsson, Biroli , Pietro, Meddens, S Fleur W, and Beauchamp, Jonathan P
Subjects: Netherlands Twin Register (NTR), Male, LD, Medizin, Poison control, Genome-wide association study, DETERMINANTS, Cathie Marsh Institute, PREFERENCES, Q1, Genome-wide association studies, HV, 0302 clinical medicine, Genetics, Behavioral/methods, GWAS, Genetics & Heredity, Genetics, 0303 health sciences, PERSONALITY, Genetic Predisposition to Disease/genetics, Behavior/physiology, Polymorphism, Single Nucleotide/genetics, 3. Good health, Manchester Institute for Collaborative Research on Ageing, Meta-analysis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Genetic Loci/genetics, Behavioural genetics, Genome-Wide Association Study/methods, Medical genetics, Female, Life Sciences & Biomedicine, Single Nucleotide/genetics, medicine.medical_specialty, ResearchInstitutes_Networks_Beacons/MICRA, Genotype, Single-nucleotide polymorphism, Genetics, Behavioral, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:330, medicine, GENDER-DIFFERENCES, SNP, Humans, Genetic Predisposition to Disease, Polymorphism, behavioural genetics, Behavioral/methods, 030304 developmental biology, Genetic association, Behavior, Science & Technology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Data Science, Case-control study, risk tolerance, GWAS, genetic architechture, Genetic Loci, Case-Control Studies, genome-wide association studies, ResearchInstitutes_Networks_Beacons/cathie_marsh_institute, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance. This research was carried out under the auspices of the Social Science Genetic Association Consortium. The research was also conducted using the UK Biobank Resource under application number 11425. The study was supported by funding from the Ragnar Söderberg Foundation (E9/11 and E42/15); the Swedish Research Council (421-2013-1061); the Jan Wallander and Tom Hedelius Foundation; an ERC Consolidator Grant to Philipp Koellinger (647648 EdGe); the Pershing Square Fund of the Foundations of Human Behavior; the Open Philanthropy Project; the National Institute on Aging, National Institutes of Health through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to the National Bureau of Economic Research and R01-AG042568-02 to the University of Southern California; the government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-152); and the Social Sciences and Humanities Research Council of Canada. We thank the International Cannabis Consortium, the eQTLgen Consortium, and the Psychiatric Genomics Consortium for sharing summary statistics from the GWAS of lifetime cannabis use, eQTL summary statistics, and summary statistics from the GWAS of ADHD, respectively. A full list of acknowledgments is provided in the Supplementary Note.
Published: 2019

19. Health status after invasive or conservative care in coronary and advanced kidney disease

Author: Spertus J. A., Jones P. G., Maron D. J., Mark D. B., O'Brien S. M., Fleg J. L., Reynolds H. R., Stone G. W., Sidhu M. S., Chaitman B. R., Chertow G. M., Hochman J. S., Bangalore S, ISCHEMIA-CKD Research Group: Abdallah M Abdallah, Abel E Moreyra, Abhay A Laddu, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Adedayo Adeboye, Agne Juceviciene, Agne Urboniene, Agnieszka Szramowska, Ahmed Abdel-Latif, Ahmed Ayoub, Ahmed Elghamaz, Ahmed Kamal, Ahmed Talaat, Ajay Sharma, Ajit Singh Narula, Akshay Bagai, Akvile Smigelskaite, Alain Raymond, Alain Rheault, Alaine Melanie Loehr, Albert Varga, Aldo P Maggioni, Alec Moorman, Alejandro Chevaile Ramos, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alexander M Chernyavskiy, Alexander Sergeevich Borisov, Alexandra Craft, Alexandra Hunter, Alexandre Ciappina Hueb, Alexandre Schaan de Quadros, Alice Manica Muller, Aline Peixoto Deiro, Allegra Stone, Almudena Castro, Amar Uxa, Amaryllis Van Craenenbroeck, Ambuj Roy, Amit Kakkar, Amy Flowers, Amy Iskandrian, Ana D Djordjevic-Dikic, Ana Gomes Almeida, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anandaroop Lahiri, Anastasia M Kuzmina-Krutetskaya, Anastasia Vamvakidou, Andras Vertes, Andre Gabriel, Andrea Bartykowszki, Andrea Lorimer, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew Starovoytov, Andrzej Łabyk, Anelise Kawakami, Angela Hoye, Angelo Nobre, Anjali Acharya, Anjali Anand, Anjana Rishmawi, Ann Banfield, Ann Luyten, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Teresinska, Anne Marie Webb, Anne Heath, Anoop Mathew, Antonia Vega, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anu Tharini, Anupama Rao, Aquiles Valdespino-Estrada, Ariel Diaz, Arif Asif, Arnold H Seto, Arturo S Campos-Santaolalla, Asim N Cheema, Asker Ahmed, Atul Mathur, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Balaji Srinivasan, Baljeet Kaur, Balram Bhargava, Bandula Guruge, Barbara Wicklund, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Benoy N Shah, Bernard de Bruyne, Beth Abramson, Beth Stefanchik, Bethany Harvey, Bharati Shivalkar, Bilal Malik, Binoy Mannekkattukudy Kurian, Bougrida Hammouche, Branko D Beleslin, Bruce Ferguson, Bruce McManus, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Carl-Éric Gagné, Carly Ohmart, Carol M Kartje, Caroline Alsweiler, Caroline Rodgers, Caroline Spindler, Carolyn J Gruber, Catherine Albert, Catherine Bone, Catherine Lemay, Cezary Kepka, Chandini Suvarna, Chantale Mercure, Charlene Wiyarand, Chetan Patel, Chiara Attanasio, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Buller, Christel Vassaliere, Christiaan Vrints, Christian Witzke, Christie Ballantyne, Christina Björklund, Christine Roraff, Christophe Laure, Christophe Thuaire, Christopher Chan, Christopher Fordyce, Christopher Kinsey, Chunli Xia, Cidney Schultz, Claes Held, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Clemens T Kadalie, Corine Thobois, Courtney Page, Cristina Bare, Dalisa Espinosa, Dan Gao, Dana Rizk, Daniela Puzhevsky, Data Analyst, David M Charytan, David O Williams, David Booth, David Charytan, David Cohen, David DeMets, David Foo, David Goldfarb, David Schlichting, David Sisson, David Taggart, David Waters, David Wheeler, David Williams, Davis Vo, Dawid Teodorczyk, Dawn D Shelstad, Dean Kereiakes, Deborah Yip, Deepa Ramaswamy, Deirdre Mattina, Deirdre Murphy, Dengke Jiang, Derek Cyr, Diana Cukali, Diane Camara, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Doreen Reimann, Doron Schwartz, Duarte Cacela, Dwayne S G Conway, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Eduardo Gomes Lima, Eduardo Hernandez-Rangel, Edward D Nicol, Edyta Kaczmarska, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise van Dongen, Elissa Restelli Piloto, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizaveta V Zbyshevskaya, Ellie Fridell, Ellis W Lader, Elvira Gosmanova, Emilie Tachot, Emma Howard, Emmanuel Sorbets, Encarnación Alonso-Álvarez, Eric Daugas, Erick Alexánderson Rosas, Estelle Montpetit, Eugene Passamani, Evgeny Shutov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, Fabio Fimiani, Fadi Hage, Fahim Haider Jafary, Fang Feng, Fatima Ranjbaran, Fausto J Pinto, Fernando Caeiro, Fernando Nolasco, Filipa Silva, Filippo Ottani, Firas Al Solaiman, Flávia Egydio, Florina Chereches, Francesca De Micco, Francesca Bianchini, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francisca Patuleia Figueiras, François Madore, Frank Harrell, Frank Rockhold, Frans Van de Werf, Franziska Guenther, Fred Mohr, G Karthikeyan, Gabriel Galeote, Gabriel Grossmann, Gabriel Steg, Gabriela Guzman, Gabriele Gabrielli, Gang Chen, Gautam Sharma, Gaylin Petty, Gelmina Mikolaitiene, Gennie Yee, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Girish Mishra, Gonzalo Barge-Caballero, Grace M Young, Graciela Scaro, Graham Wong, Gregg Pressman, Gregor Simonis, Gudrun Steinmaurer, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillermo Garcia-Garcia, Guoqin Wang, Gurpreet S Wander, Gurpreet Gulati, Haibo Zhang, Halina Marciniak, Hao Dai, Haojian Dong, Harold Franch, Harvey White, Hatem Elabd, Hayley Pomeroy, Heather Golden, Heidi Wilson, Helene Abergel, Hemalata Siddaram, Hemant Shakhar Mahapatra, Henry C Stokes, Hermine Osseni, Herwig Schuchlenz, Hicham Skali, Holly Mattix-Kramer, Hong Cheng, Hossam Mahrous, Hristo Pejkov, Hugo Marques, Hui Zhong, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ikraam Hassan, Ileana L Pina, Ilona Tamasauskiene, Inês Zimbarra Cabrita, Ines Rodrigues, Inga Soveri, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Isabelle Roy, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, Jacek Kusmierek, Jackie Chow, Jaekyeong Heo, Jakub Maksym, James E Davies, James J Jang, James Hirsch, James Tatoulis, Jan Henzel, Janaina Oliveira, Janani Rangaswami, Jane Eckstein, Janitha Raj, Jaqueline Pozzibon, Jaroslaw Drozdz, Jason Loh Kwok Kong, Jason T Call, Jason Linefsky, Javier J Garcia, Jay Meisner, Jayne Scales, Jean Michel Juliard, Jean Diodati, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeff Leimberger, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Stojkovic, Jenne M Jose, Jennifer L Stanford, Jennifer Hogan, Jennifer Horst, Jennifer Isaacs, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jerry Yee, Jessica Berg, Jesus Peteiro, Jesús Peteiro, Jia Li, Jiamin Liu, Jianxin Zhang, Jill Marcus, Jim Blankenship, Jing Dong, Jiyan Chen, Jo Evans, Joaquín V Peñafiel, Joe Sabik, Johann Christopher, John B Kostis, John Joseph Graham, John Doan, John Jose, John Kotter, John Lehman, John Middleton, John Pownall, Jonathan M Gleadle, Jonathan S Chavez-Iñiguez, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Lebowitz, Jonean Thorsen, Jorge Carrillo Calvillo, Jorge Escobedo, José A Ortega-Ramírez, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Costa Vieira, José M Flores-Palacios, Jose Fragata, Jose Lopes, Jose Lopez-Sendon, José Lopez-Sendon, Jose Rueda, Joseph B Selvanayagam, Joseph Sacco, Joshua P Loh, Joy Burkhardt, Juan Manuel López Quijano, Juan Gaztanaga, Judit Sebo, Judith Wright, Juergen Stumpf, Julia de Aveiro Morata, Julio César Figal, Julio Hernandez Jaras, Junqing Yang, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Karen Calfas, Karen Petrosyan, Karen Servilla, Karen Swan, Karin Ploetze, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Katharina Knaut, Katherine Martin, Kathleen Claes, Kathryn Mason, Ken Mahaffey, Kenneth Gin, Kerry Lee, Kerstin Bonin, Kerstin Mikes, Kevin R Bainey, Kevin T Harley, Kevin Marzo, Kevin McMahon, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khrystyna Kushniriuk, Kian-Keong Poh, Kim Holland, Kimberly E Halverson, Kinnari Murphy, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kreton Mavromatis, Krishnakumar Hongalgi, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristine Arges, Kristine Teoh, Krzysztof Drzymalski, Lalathaksha Kumbar, Laszlone Matics, LaTonya J Hickson, Laura Keinaite, Laura Sarti, Laura True, Lawrence M Phillips, Lawrence Friedman, Leandro C Maranan, Leda Lotaif, Lekshmi Dharmarajan, Leo A Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Li Hai Yan, Li Li, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilian Mazza Barbosa, Liljana Tozija, Linda Arcand, Lino Patricio, Liping Zhang, Lisa Hatch, Lixin Jiang, Liz Low, Loay Salman, Lorena Lopez, Lori Pritchard, Luis Bernanrdes, Luis Guzman, Lynette L Teo, M Sowjanya Reddy, Maarten Simoons, Maayan Konigstein, Mafalda Selas, Magdalena Madero, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdy Abdelhamid, Magid Fahim, Mahevamma Mylarappa, Majo X Joseph, Malgorzata Frach, Manjula Rani, Marcello Galvani, Marcin Demkow, Marcin Szkopiak, Marco De Fabritis, Marco Magnoni, Marco Marini, Marco Sicuro, Marek Roik, Maria A Alfonso, Maria Antonieta Pereira de Moraes, María Dolores Martínez-Ruíz, Maria Eugenia Canziani, Maria Eugenia Martin, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Andreasson, Maria Posada, Marianna D A Dracoulakis, Mariano Rubio, Marija T Petrovic, Marina Vieira, Mario J Garcia, Mario D'arezzo, Maris Orgera, Marius Miglinas, Mark Garand, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Swiderek, Martha Meyer, Martina Ceseri, Martinia Tricoli, Mary Wiilliams, Mary Ann Champagne, Mary Streif, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Shinseki, Matthew Weir, Maura Carina Nédio, Max-Paul Winter, Mayil S Krishnam, Meenakshi Mishra, Mei Hwang, Melemadathil Srilatha, Melissa LeFevre, Mengistu Simegn, Michael A Gibson, Michael B Rubens, Michael D Shapiro, Michael Chobanian, Michael Davidson, Michael Farkouh, Michael Mack, Michal Wlodarczyk, Michel G Khouri, Michelle Crowder, Michelle Ratliff, Miguel Borges Santos, Miguel Nobre Menezes, Miguel Perez Fontan, Miguel Barrero, Mihaly Tapolyai, Mikhail T Torosoff, Milan R Dobric, Milind Avdhoot Gadkari, Min Tun Kyaw, Miri Revivo, Mitchel B Lustre, Mohamed Adel, Mohamed Hassan, Mohammad El-Hajjar, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Monika Laukyte, Muhamed Saric, Myrthes Emy Takiuti, Nadia Asif, Nagaraja Moorthy, Naima L Ogletree, Nana O Katamadze, Nandita Nataraj, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Nathalie Brosens, Naved Aslam, Naveed Akhtar, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Neesh Pannu, Neill Duncan, Nevena Garcevic, Ngaire Meadows, Nicholas Danchin, Nicole Deming, Nikola N Boskovic, Nikolaos Karogiannis, Ning Zhang, Nirmal Kumar, Niruta Sharma, Nitika Chadha, Nitish Naik, Noelle M Durfee, Nora M Cosgrove, Norbert Urbanski, Norma Hogg, Olga Walesiak, Olga Zdończyk, Olga Zhdanova, Olivia Anaya, Olugbenga Bello, Omar Almousalli, Omar Thompson, Orit Kliuk, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, Pablo Raffaele, Page Salanger, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Ouyang, Pamela Woodard, Paola Emanuela Poggio Smanio, Paola Smanio, Paolo Calabro, Patricia K Nguyen, Patricia Alarie, Patricia Carrilho, Patricia Endsley, Patricia Pellikka, Patrycja Lebioda, Paul Der Mesropian, Paul Hauptman, Paula García-González, Paula Wilson, Paulo Cury Rezende, Paulo Novis Rocha, Pedro Canas Silva, Pedro Farto E Abreu, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peiyu He, Peter A McCullough, Peter H Stone, Peter Douglass, Peter Sizeland, Peter Voros, Philippe Gabriel Steg, Philippe Genereux, Philippe Généreux, Philippe Menasche, Philippe Rheault, Piero Tassinario, Pierre Gervais, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Poay-Huan Loh, Pouneh Samadi, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puneet Sodhi, Pushpa Naik, Qi Zhong, Qian Zhao, Qianqian Yuan, Qiulan Xie, Rachel Murphy, Radmila Lyubarova, Radmilar Lyubarova, Raewyn Fisher, Rafael Diaz, Rafael Maldonado, Rafael Selgas, Raffaele Bugiardini, Rafia Chaudhry, Raisa Kavalakkat, Rajalekshmi Vs, Rajesh Gopalan Nair, Rajiv Narang, Rakesh Yadav, Ramiro Carvalho, Ramon de Jesús-Pérez, Ran Leng, Ranjan Kachru, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Reinette Hampson, Renato Abdala Karam Kalil, Renato D Lopes, Renato George Eick, Renato Lopes, Reshma Ravindran, Reto Andreas Gamma, Ricardo Costa, Richa Bhatt, Richard H J Trimlett, Risha Patel, Rita Coram, Robert K Riezebos, Robert M Donnino, Robert Guyton, Robert Harrington, Robert Malecki, Roberto René Favaloro, Robyn Elliott, Rodolfo G S D Lima, Rohit Tandon, Rolf Doerr, Roma Tewari, Ron Wald, Rongrong Hu, Rory Collins, Roxana Mehran, Roxy Senior, Rubén Baleón-Espinosa, Ruben Ramos, Rui Ferreira, Ruth Kirby, Ruth Pérez-Fernández, S Ramakrishnan, S K Dwivedi, Sadath Lubna, Sadiq Ahmed, Sajeev Chakanalil Govindan, Salamah Alfalahi, Salvador Cruz-Flores, Salvatore P Costa, Sampoornima Setty, Samuel Nwosu, Sandeep Mahajan, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandy Carr, Sanja Simic Ogrizovic, Sanja Ogrizovic, Sanjeev Gulati, Sanjeev Sharma, Sara Fernandez, Sarah Williams, Sarju Ralhan, Sasko Kedev, Satinder Singh, Satish Sankaranarayanan, Satvic Cholenahally Manjunath, Sau Lee, Schawana Thaxton, Sean M O'Brien, Sebastian Sobczak, Seema Nour, Sergey A Sayganov, Sérgio Bravo Baptista, Sergio Draibe, Seth Sokol, Sharad Chandra, Shari Mackedanz, Shaun Goodman, Shayan Shirazian, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shruti Pandey, Shuyang Zhang, 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H.R., Stone G.W., Sidhu M.S., Chaitman B.R., Chertow G.M., Hochman J.S., Bangalore S, and ISCHEMIA-CKD Research Group: Abdallah M Abdallah, Abel E Moreyra, Abhay A Laddu, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Adedayo Adeboye, Agne Juceviciene, Agne Urboniene, Agnieszka Szramowska, Ahmed Abdel-Latif, Ahmed Ayoub, Ahmed Elghamaz, Ahmed Kamal, Ahmed Talaat, Ajay Sharma, Ajit Singh Narula, Akshay Bagai, Akvile Smigelskaite, Alain Raymond, Alain Rheault, Alaine Melanie Loehr, Albert Varga, Aldo P Maggioni, Alec Moorman, Alejandro Chevaile Ramos, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alexander M Chernyavskiy, Alexander Sergeevich Borisov, Alexandra Craft, Alexandra Hunter, Alexandre Ciappina Hueb, Alexandre Schaan de Quadros, Alice Manica Muller, Aline Peixoto Deiro, Allegra Stone, Almudena Castro, Amar Uxa, Amaryllis Van Craenenbroeck, Ambuj Roy, Amit Kakkar, Amy Flowers, Amy Iskandrian, Ana D Djordjevic-Dikic, Ana Gomes Almeida, Ana Rita Francisco, 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Bare, Dalisa Espinosa, Dan Gao, Dana Rizk, Daniela Puzhevsky, Data Analyst, David M Charytan, David O Williams, David Booth, David Charytan, David Cohen, David DeMets, David Foo, David Goldfarb, David Schlichting, David Sisson, David Taggart, David Waters, David Wheeler, David Williams, Davis Vo, Dawid Teodorczyk, Dawn D Shelstad, Dean Kereiakes, Deborah Yip, Deepa Ramaswamy, Deirdre Mattina, Deirdre Murphy, Dengke Jiang, Derek Cyr, Diana Cukali, Diane Camara, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Doreen Reimann, Doron Schwartz, Duarte Cacela, Dwayne S G Conway, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Eduardo Gomes Lima, Eduardo Hernandez-Rangel, Edward D Nicol, Edyta Kaczmarska, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise van Dongen, Elissa Restelli Piloto, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizaveta V Zbyshevskaya, Ellie Fridell, Ellis W Lader, Elvira Gosmanova, Emilie Tachot, Emma Howard, Emmanuel Sorbets, Encarnación Alonso-Álvarez, Eric Daugas, Erick Alexánderson Rosas, Estelle Montpetit, Eugene Passamani, Evgeny Shutov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, Fabio Fimiani, Fadi Hage, Fahim Haider Jafary, Fang Feng, Fatima Ranjbaran, Fausto J Pinto, Fernando Caeiro, Fernando Nolasco, Filipa Silva, Filippo Ottani, Firas Al Solaiman, Flávia Egydio, Florina Chereches, Francesca De Micco, Francesca Bianchini, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francisca Patuleia Figueiras, François Madore, Frank Harrell, Frank Rockhold, Frans Van de Werf, Franziska Guenther, Fred Mohr, G Karthikeyan, Gabriel Galeote, Gabriel Grossmann, Gabriel Steg, Gabriela Guzman, Gabriele Gabrielli, Gang Chen, Gautam Sharma, Gaylin Petty, Gelmina Mikolaitiene, Gennie Yee, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Girish Mishra, Gonzalo Barge-Caballero, Grace M Young, Graciela Scaro, Graham Wong, Gregg Pressman, Gregor Simonis, Gudrun Steinmaurer, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillermo Garcia-Garcia, Guoqin Wang, Gurpreet S Wander, Gurpreet Gulati, Haibo Zhang, Halina Marciniak, Hao Dai, Haojian Dong, Harold Franch, Harvey White, Hatem Elabd, Hayley Pomeroy, Heather Golden, Heidi Wilson, Helene Abergel, Hemalata Siddaram, Hemant Shakhar Mahapatra, Henry C Stokes, Hermine Osseni, Herwig Schuchlenz, Hicham Skali, Holly Mattix-Kramer, Hong Cheng, Hossam Mahrous, Hristo Pejkov, Hugo Marques, Hui Zhong, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ikraam Hassan, Ileana L Pina, Ilona Tamasauskiene, Inês Zimbarra Cabrita, Ines Rodrigues, Inga Soveri, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Isabelle Roy, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, Jacek Kusmierek, Jackie Chow, Jaekyeong Heo, Jakub Maksym, James E Davies, James J Jang, James Hirsch, James Tatoulis, Jan Henzel, Janaina Oliveira, Janani Rangaswami, Jane Eckstein, Janitha Raj, Jaqueline Pozzibon, Jaroslaw Drozdz, Jason Loh Kwok Kong, Jason T Call, Jason Linefsky, Javier J Garcia, Jay Meisner, Jayne Scales, Jean Michel Juliard, Jean Diodati, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeff Leimberger, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Stojkovic, Jenne M Jose, Jennifer L Stanford, Jennifer Hogan, Jennifer Horst, Jennifer Isaacs, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jerry Yee, Jessica Berg, Jesus Peteiro, Jesús Peteiro, Jia Li, Jiamin Liu, Jianxin Zhang, Jill Marcus, Jim Blankenship, Jing Dong, Jiyan Chen, Jo Evans, Joaquín V Peñafiel, Joe Sabik, Johann Christopher, John B Kostis, John Joseph Graham, John Doan, John Jose, John Kotter, John Lehman, John Middleton, John Pownall, Jonathan M Gleadle, Jonathan S Chavez-Iñiguez, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Lebowitz, Jonean Thorsen, Jorge Carrillo Calvillo, Jorge Escobedo, José A Ortega-Ramírez, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Costa Vieira, José M Flores-Palacios, Jose Fragata, Jose Lopes, Jose Lopez-Sendon, José Lopez-Sendon, Jose Rueda, Joseph B Selvanayagam, Joseph Sacco, Joshua P Loh, Joy Burkhardt, Juan Manuel López Quijano, Juan Gaztanaga, Judit Sebo, Judith Wright, Juergen Stumpf, Julia de Aveiro Morata, Julio César Figal, Julio Hernandez Jaras, Junqing Yang, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Karen Calfas, Karen Petrosyan, Karen Servilla, Karen Swan, Karin Ploetze, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Katharina Knaut, Katherine Martin, Kathleen Claes, Kathryn Mason, Ken Mahaffey, Kenneth Gin, Kerry Lee, Kerstin Bonin, Kerstin Mikes, Kevin R Bainey, Kevin T Harley, Kevin Marzo, Kevin McMahon, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khrystyna Kushniriuk, Kian-Keong Poh, Kim Holland, Kimberly E Halverson, Kinnari Murphy, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kreton Mavromatis, Krishnakumar Hongalgi, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristine Arges, Kristine Teoh, Krzysztof Drzymalski, Lalathaksha Kumbar, Laszlone Matics, LaTonya J Hickson, Laura Keinaite, Laura Sarti, Laura True, Lawrence M Phillips, Lawrence Friedman, Leandro C Maranan, Leda Lotaif, Lekshmi Dharmarajan, Leo A Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Li Hai Yan, Li Li, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilian Mazza Barbosa, Liljana Tozija, Linda Arcand, Lino Patricio, Liping Zhang, Lisa Hatch, Lixin Jiang, Liz Low, Loay Salman, Lorena Lopez, Lori Pritchard, Luis Bernanrdes, Luis Guzman, Lynette L Teo, M Sowjanya Reddy, Maarten Simoons, Maayan Konigstein, Mafalda Selas, Magdalena Madero, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdy Abdelhamid, Magid Fahim, Mahevamma Mylarappa, Majo X Joseph, Malgorzata Frach, Manjula Rani, Marcello Galvani, Marcin Demkow, Marcin Szkopiak, Marco De Fabritis, Marco Magnoni, Marco Marini, Marco Sicuro, Marek Roik, Maria A Alfonso, Maria Antonieta Pereira de Moraes, María Dolores Martínez-Ruíz, Maria Eugenia Canziani, Maria Eugenia Martin, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Andreasson, Maria Posada, Marianna D A Dracoulakis, Mariano Rubio, Marija T Petrovic, Marina Vieira, Mario J Garcia, Mario D'arezzo, Maris Orgera, Marius Miglinas, Mark Garand, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Swiderek, Martha Meyer, Martina Ceseri, Martinia Tricoli, Mary Wiilliams, Mary Ann Champagne, Mary Streif, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Shinseki, Matthew Weir, Maura Carina Nédio, Max-Paul Winter, Mayil S Krishnam, Meenakshi Mishra, Mei Hwang, Melemadathil Srilatha, Melissa LeFevre, Mengistu Simegn, Michael A Gibson, Michael B Rubens, Michael D Shapiro, Michael Chobanian, Michael Davidson, Michael Farkouh, Michael Mack, Michal Wlodarczyk, Michel G Khouri, Michelle Crowder, Michelle Ratliff, Miguel Borges Santos, Miguel Nobre Menezes, Miguel Perez Fontan, Miguel Barrero, Mihaly Tapolyai, Mikhail T Torosoff, Milan R Dobric, Milind Avdhoot Gadkari, Min Tun Kyaw, Miri Revivo, Mitchel B Lustre, Mohamed Adel, Mohamed Hassan, Mohammad El-Hajjar, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Monika Laukyte, Muhamed Saric, Myrthes Emy Takiuti, Nadia Asif, Nagaraja Moorthy, Naima L Ogletree, Nana O Katamadze, Nandita Nataraj, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Nathalie Brosens, Naved Aslam, Naveed Akhtar, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Neesh Pannu, Neill Duncan, Nevena Garcevic, Ngaire Meadows, Nicholas Danchin, Nicole Deming, Nikola N Boskovic, Nikolaos Karogiannis, Ning Zhang, Nirmal Kumar, Niruta Sharma, Nitika Chadha, Nitish Naik, Noelle M Durfee, Nora M Cosgrove, Norbert Urbanski, Norma Hogg, Olga Walesiak, Olga Zdończyk, Olga Zhdanova, Olivia Anaya, Olugbenga Bello, Omar Almousalli, Omar Thompson, Orit Kliuk, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, Pablo Raffaele, Page Salanger, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Ouyang, Pamela Woodard, Paola Emanuela Poggio Smanio, Paola Smanio, Paolo Calabro, Patricia K Nguyen, Patricia Alarie, Patricia Carrilho, Patricia Endsley, Patricia Pellikka, Patrycja Lebioda, Paul Der Mesropian, Paul Hauptman, Paula García-González, Paula Wilson, Paulo Cury Rezende, Paulo Novis Rocha, Pedro Canas Silva, Pedro Farto E Abreu, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peiyu He, Peter A McCullough, Peter H Stone, Peter Douglass, Peter Sizeland, Peter Voros, Philippe Gabriel Steg, Philippe Genereux, Philippe Généreux, Philippe Menasche, Philippe Rheault, Piero Tassinario, Pierre Gervais, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Poay-Huan Loh, Pouneh Samadi, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puneet Sodhi, Pushpa Naik, Qi Zhong, Qian Zhao, Qianqian Yuan, Qiulan Xie, Rachel Murphy, Radmila Lyubarova, Radmilar Lyubarova, Raewyn Fisher, Rafael Diaz, Rafael Maldonado, Rafael Selgas, Raffaele Bugiardini, Rafia Chaudhry, Raisa Kavalakkat, Rajalekshmi Vs, Rajesh Gopalan Nair, Rajiv Narang, Rakesh Yadav, Ramiro Carvalho, Ramon de Jesús-Pérez, Ran Leng, Ranjan Kachru, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Reinette Hampson, Renato Abdala Karam Kalil, Renato D Lopes, Renato George Eick, Renato Lopes, Reshma Ravindran, Reto Andreas Gamma, Ricardo Costa, Richa Bhatt, Richard H J Trimlett, Risha Patel, Rita Coram, Robert K Riezebos, Robert M Donnino, Robert Guyton, Robert Harrington, Robert Malecki, Roberto René Favaloro, Robyn Elliott, Rodolfo G S D Lima, Rohit Tandon, Rolf Doerr, Roma Tewari, Ron Wald, Rongrong Hu, Rory Collins, Roxana Mehran, Roxy Senior, Rubén Baleón-Espinosa, Ruben Ramos, Rui Ferreira, Ruth Kirby, Ruth Pérez-Fernández, S Ramakrishnan, S K Dwivedi, Sadath Lubna, Sadiq Ahmed, Sajeev Chakanalil Govindan, Salamah Alfalahi, Salvador Cruz-Flores, Salvatore P Costa, Sampoornima Setty, Samuel Nwosu, Sandeep Mahajan, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandy Carr, Sanja Simic Ogrizovic, Sanja Ogrizovic, Sanjeev Gulati, Sanjeev Sharma, Sara Fernandez, Sarah Williams, Sarju Ralhan, Sasko Kedev, Satinder Singh, Satish Sankaranarayanan, Satvic Cholenahally Manjunath, Sau Lee, Schawana Thaxton, Sean M O'Brien, Sebastian Sobczak, Seema Nour, Sergey A Sayganov, Sérgio Bravo Baptista, Sergio Draibe, Seth Sokol, Sharad Chandra, Shari Mackedanz, Shaun Goodman, Shayan Shirazian, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shruti Pandey, Shuyang Zhang, Siddharth Gadage, Sik-Yin V Tan, Sílvia Zottis Poletti, Silvia Valbuena, Simone Savaris, Solomon Yakubov, Songlin Zhu, Sonika Gupta, Sorin Brener, Sothinathan Gurunathan, Soundarya Nayak, Sowjanya Reddy, Stanley E Cobos, Stefan Weikl, Stephanie M Lane, Stephanie Ferket, Stephanie Mavromichalis, Stephen Fremes, Steven A Fein, Steven P Sedlis, Steven Giovannone, Steven Weitz, Subhash Banerjee, Sudhanva S Hegde, Suellen Hosino, Sulagna Mookherjee, Suman Singh, Sumith Abeygunasekara, Sundeep Mishra, Sunil Kumar Verma, Suresh Kumar, Suryaprakash Narayanappa, Susan K Milbrandt, Susana Silva, Susanna Stevens, Suvarna Kolhe, Suzana Tavares, Suzanne Welsh, T A Kishore, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarek Rashid, Tarun K Mittal, Tauane Bello Duarte, Téodora Dutoiu, Teresa Delgadillo, Terrance Chua, Terrance Welch, Theodoros Kofidis, Thierry Lefevre, Tiago Silva, Timea Boros, Titus Lau, Tiziana Formisano, Tomasz Ciurus, Tomasz Tarchalski, Tracy Tan, Umesh Lingaraj, V K Bahl, V S Narain, Valentina Pellu, Valentine Lobo, Valerie Robesyn, Vandana Yadav, Veerabhadra Gupta, Verghese Mathew, Vicente Miro, Victoria Gumerova, Victoria Hernandez, Vijay Kher, Vijay Kumar, Vikas Makkar, Vikranth Reddy, Viktoria Bulkley, Vinoi George David, Virendra Misra, Virginia Fernández-Figares, Vladimir Ryasniansky, Vojislav L Giga, Wael A Almahmeed, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Wayne Pennachi, Wei Ling Lau, Weibing Xing, Weijing Bian, Wendy L Stewart, Wendy Drewes, Whady Hueb, William Weintraub, Winnie C Sia, Xacobe Flores-Ríos, Xiang Ma, Xiangqiong Gu, Xiaomei Li, Xiaoyi Xu, Xin Fu, Xuemei Li, Xutong Wang, Yanek Pépin-Dubois, Yaron Arbel, Yechen Han, Yiming Lit, Ying Tung Sia, Ying Wang, Yining Yang, Yitong Ma, Yolayfi Peralta, Yves Smets, Yvonne Taul, Zalina Kudzoeva, Zeljko Z Markovic, Zhangsuo Liu, Zhenyu Liu, Zhiming Ye, Zixiang Yu, Zoltan Davidovits, Zvezdana Petronijevic
Subjects: Male, Intention to Treat Analysi, medicine.medical_treatment, Health Status, Myocardial Ischemia, 030204 cardiovascular system & hematology, Coronary Angiography, law.invention, Health Statu, 0302 clinical medicine, Randomized controlled trial, law, Surveys and Questionnaires, Odds Ratio, Surveys and Questionnaire, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, medicine.diagnostic_test, General Medicine, Middle Aged, Intention to Treat Analysis, Cardiology, Female, Human, medicine.medical_specialty, Revascularization, Follow-Up Studie, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, medicine, Humans, cardiovascular diseases, Healthy Lifestyle, Renal Insufficiency, Chronic, Proportional Hazards Models, Aged, Intention-to-treat analysis, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Odds ratio, medicine.disease, Angiography, Exercise Test, Proportional Hazards Model, business, Kidney disease, Follow-Up Studies
Abstract: BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of
Published: 2020

20. Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study

Author: James K. Min, Roxy Senior, Michel G. Khouri, Khaled Abdul-Nour, Yi Li, Michael H. Picard, Leonid Bershtein, Khaled Alfakih, Kian Keong Poh, Michael D. Shapiro, Mark de Belder, David J. Maron, Harmony R. Reynolds, Mohammad El-Hajjar, Judith S. Hochman, John A. Spertus, Jelena Celutkiene, Rebecca Anthopolos, John F. Beltrame, Jesús Peteiro, Patricia A. Pellikka, José Luis López Sendón, Dennis Kunichoff, and Jerome L. Fleg
Subjects: Male, medicine.medical_specialty, business.industry, Ischemia, Microvascular angina, Coronary Artery Disease, Middle Aged, medicine.disease, Natural history, Coronary artery disease, Physiology (medical), Internal medicine, medicine, Cardiology, Humans, Female, cardiovascular diseases, Cardiology and Cardiovascular Medicine, business, Aged, Natural History
Abstract: Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P P =0.46) or ISCHEMIA stress echocardiography participants ( P =0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). Conclusions: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02347215.
Published: 2021

21. A Pre-Phase III Efficacy Trial of the Spermicide/Contraceptive Effect of the Invisible Condom, a Non-Hormonal Vaginal Gel, in Women from Canada

Author: Madeleine Lemyre, Sylvie Trottier, Isabelle Chabot, Michel G. Bergeron, Rabeea F. Omar, André Ulmann, and Mathieu Leboeuf
Subjects: Adult, Male, medicine.medical_specialty, Canada, Adolescent, media_common.quotation_subject, law.invention, Condoms, Young Adult, Condom, Contraceptive Agents, law, Pregnancy, medicine, Humans, Ovulation, Sperm motility, media_common, Obstetrics, business.industry, Spermicide, Vaginal gel, Obstetrics and Gynecology, Middle Aged, Sperm, Sexual intercourse, Sperm Motility, Vaginal Creams, Foams, and Jellies, Contraceptive Effect, Female, business
Abstract: Objectives To evaluate the spermicidal efficacy of non-hormonal vaginal gel in vitro and in a post-coital test, and to evaluate its contraceptive efficacy in Canadian women of childbearing age. Methods We conducted single-centre trial to assess spermicidal and contraceptive efficacy of vaginal gel. Participants were healthy, sexually active women aged 18–49 years and their regular male sexual partners (30 couples). Measured outcomes included effect of vaginal gel on sperm motility in vitro, its effect on sperm in a post-coital test, and its effect on pregnancy prevention over 3 months. Results For in vitro spermicidal effect, 98% and 67% of sperm were immotile in the presence of the gel with sodium lauryl sulfate (gel-SLS) and gel alone, respectively. For the post-coital test, 99% and 93% of sperm were immotile in the presence of gel-SLS and gel alone, respectively. In the second part of trial, a total of 410 instances of vaginal intercourse in 95 menstrual cycles were protected (during 3-month period of gel-SLS use before each sexual intercourse with probability of 24 conceptions prevented according to Wilcox's table). Four women became pregnant during the study period; 2 during unprotected vaginal intercourse around the time of ovulation, and 2 attributed to user failure. Conclusion Based on our results, the vaginal gel demonstrated important spermicidal and contraceptive effect. A larger phase III contraceptive efficacy trial is warranted. The vaginal gel may represent a non-hormonal spermicide/contraceptive option for women.
Published: 2021

22. Loss of dystrophin expression in skeletal muscle is associated with senescence of macrophages and endothelial cells

Author: Sean Y. Ng, Adam P. W. Johnston, Athan G. Dial, Craig S. Campbell, Laura V. Young, Catherine A. Bellissimo, Michel G. Arsenault, Christopher G. R. Perry, Emma C. Moore, Vladimir Ljubicic, and William Morrison
Subjects: 0301 basic medicine, Senescence, Cyclin-Dependent Kinase Inhibitor p21, Male, Physiology, Duchenne muscular dystrophy, Dystrophin, 03 medical and health sciences, Mice, 0302 clinical medicine, Myofibrils, medicine, Animals, Humans, Secretion, Muscular dystrophy, Muscle, Skeletal, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, biology, Regeneration (biology), Macrophages, Skeletal muscle, Endothelial Cells, Cell Biology, Cell cycle, Muscular Dystrophy, Animal, medicine.disease, beta-Galactosidase, Cell biology, Mice, Inbred C57BL, Muscular Dystrophy, Duchenne, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, biology.protein, Mice, Inbred mdx, Tumor Suppressor Protein p53, 030217 neurology & neurosurgery, Signal Transduction
Abstract: Cellular senescence is the irreversible arrest of normally dividing cells and is driven by cell cycle inhibitory proteins such as p16, p21 and p53. When cells enter senescence, they secrete a host of proinflammatory factors known as the senescence associated secretory phenotype which has deleterious effects on surrounding cells and tissues. Little is known of the role of senescence in Duchenne Muscular Dystrophy (DMD), the fatal X-linked neuromuscular disorder typified by chronic inflammation, extracellular matrix remodeling and a progressive loss in muscle mass and function. Here, we demonstrate using C57-mdx (8-week-old) and D2-mdx mice (4-week and 8-week-old), two mouse models of DMD, that cells displaying canonical markers of senescence are found within skeletal muscle. 8-week-old D2-mdx mice, which display severe muscle pathology, had greater numbers of senescent cells associated with areas of inflammation which were mostly Cdkn1a-positive macrophages while in C57-mdx muscle, senescent populations were endothelial cells and macrophages localized to newly regenerated myofibers. Interestingly, this pattern was similar to cardiotoxin (CTX)-injured wildtype (WT) muscle which experienced a transient senescent response. Dystrophic muscle demonstrated significant upregulations in senescence pathway genes (Cdkn1a (p21), Cdkn2a (p16INK4A), Trp53 (p53)) which correlated with the quantity of SA-b-Gal-positive cells. These results highlight an underexplored role for cellular senescence in murine dystrophic muscle.
Published: 2021

23. Genetic analyses identify widespread sex-differential participation bias

Author: Pirastu, Nicola, Cordioli, Mattia, Nandakumar, Priyanka, Mignogna, Gianmarco, Abdellaoui, Abdel, Hollis, Benjamin, Kanai, Masahiro, Rajagopal, Veera M, Parolo, Pietro Della Briotta, Baya, Nikolas, Carey, Caitlin E, Karjalainen, Juha, Als, Thomas D, Van Der Zee, Matthijs D, Day, Felix R, Ong, Ken K, FinnGen Study, 23andMe Research Team, IPSYCH Consortium, Morisaki, Takayuki, De Geus, Eco, Bellocco, Rino, Okada, Yukinori, Børglum, Anders D, Joshi, Peter, Auton, Adam, Hinds, David, Neale, Benjamin M, Walters, Raymond K, Nivard, Michel G, Perry, John RB, Ganna, Andrea, Pirastu, Nicola [0000-0002-5363-3886], Cordioli, Mattia [0000-0002-4872-0520], Mignogna, Gianmarco [0000-0002-3989-7180], Abdellaoui, Abdel [0000-0003-1088-6784], Kanai, Masahiro [0000-0001-5165-4408], Rajagopal, Veera M [0000-0002-5236-168X], Baya, Nikolas [0000-0002-4681-374X], Als, Thomas D [0000-0002-2963-1928], Van der Zee, Matthijs D [0000-0003-4076-9167], Day, Felix R [0000-0003-3789-7651], Ong, Ken K [0000-0003-4689-7530], Okada, Yukinori [0000-0002-0311-8472], Børglum, Anders D [0000-0001-8627-7219], Joshi, Peter [0000-0002-6361-5059], Hinds, David [0000-0002-4911-803X], Neale, Benjamin M [0000-0003-1513-6077], Walters, Raymond K [0000-0001-8422-6530], Perry, John RB [0000-0001-6483-3771], Ganna, Andrea [0000-0002-8147-240X], and Apollo - University of Cambridge Repository
Subjects: Adult, Male, Sex Characteristics, Inheritance Patterns, Polymorphism, Single Nucleotide, United Kingdom, Bias, Genetic Loci, Sample Size, Chromosomes, Human, Humans, Female, Artifacts, Biological Specimen Banks, Genome-Wide Association Study
Abstract: Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index-increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10-36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.
Published: 2021

24. Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness

Author: Abraham A. Palmer, Dorret I. Boomsma, Sandra Sanchez-Roige, Jouke-Jan Hottenga, Alexander Neumann, Stephanie Cacioppo, Damiaan Denys, Gonneke Willemsen, Jorien L. Treur, Abdel Abdellaoui, Najaf Amin, Michel G. Nivard, Miriam A. Mosing, John T. Cacioppo, Julia Sealock, Bart M. L. Baselmans, Hill F. Ip, Karin J. H. Verweij, I. Szilagyi, Jessica Dennis, Sarah L. Elson, Henning Tiemeier, Matthijs D. van der Zee, Yi Lu, Cornelia M. van Duijn, Pierre Fontanillas, Lea K. Davis, Nancy L. Pedersen, Epidemiology, Psychiatry, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, APH - Mental Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Social Psychology, and APH - Methodology
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Male, Multifactorial Inheritance, Genotype, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Mendelian randomization, Genetics, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Phenomics, Association Studies Article, Molecular Biology, Genetics (clinical), Loneliness, Mental Disorders, Mendelian Randomization Analysis, General Medicine, Mental health, Genetic architecture, 3. Good health, 030104 developmental biology, Mental Health, Phenotype, Health, Marital status, Female, medicine.symptom, 030217 neurology & neurosurgery, Clinical psychology, Genome-Wide Association Study
Abstract: Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. Although the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. Although it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition toward loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with EHR data to conduct a PheWAS with. A genetic predisposition toward loneliness was associated with cardiovascular, psychiatric, and metabolic disorders and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, the effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.
Published: 2019

25. Associations between Loneliness and Personality are Mostly Driven by a Genetic Association with Neuroticism

Author: Gareth E. Davies, John T. Cacioppo, Eco J. C. de Geus, Gonneke Willemsen, Hsi-Yuan Chen, Erik A. Ehli, Michel G. Nivard, Abdel Abdellaoui, Karin J. H. Verweij, Dorret I. Boomsma, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Methodology, and Adult Psychiatry
Subjects: Adult, Male, 0301 basic medicine, Netherlands Twin Register (NTR), Adolescent, Social Psychology, media_common.quotation_subject, 050109 social psychology, Polymorphism, Single Nucleotide, Genetic correlation, Article, Young Adult, 03 medical and health sciences, medicine, Humans, Personality, 0501 psychology and cognitive sciences, Longitudinal Studies, Registries, Big Five personality traits, Aged, Netherlands, media_common, Aged, 80 and over, Neuroticism, Extraversion and introversion, Loneliness, 05 social sciences, Assortative mating, SDG 10 - Reduced Inequalities, Middle Aged, Twin study, Phenotype, 030104 developmental biology, Female, medicine.symptom, Psychology, Clinical psychology
Abstract: OBJECTIVE: Loneliness is an aversive response to a discrepancy between desired and actual social relationships and correlates with personality. We investigate the relationship of loneliness and personality in twin-family and molecular genetic data.METHOD: Phenotypic correlations between loneliness and the Big Five personality traits were estimated in 29,625 adults, and in a group with genome-wide genotype data (N=4,222), genetic correlations were obtained. We explored whether genetic correlations may reflect causal relationships by investigating within monozygotic twin-pair differences (Npairs =2,662), by longitudinal within-subject changes in personality and loneliness (N=4,260-9,238 longitudinal comparisons), and by longitudinal cross-lagged panel analyses (N=15,628). Finally, we tested whether genetic correlations were due to cross-trait assortative mating (Nspouse-pairs =4,436).RESULTS: The strongest correlations with loneliness were observed for neuroticism (r=.55) and extraversion (r=-.33). Only neuroticism showed a high correlation with loneliness independent of other personality traits (r=.50), so follow-up analyses focused on neuroticism. The genetic correlation between loneliness and neuroticism from genotyped variants was .71; a significant reciprocal causal relationship and non-significant cross-trait assortative mating imply that this is at least partly due to mediated pleiotropy.CONCLUSION: We show that the relationship between loneliness and personality is largely explained by its relationship with neuroticism, which is substantially genetic in nature. This article is protected by copyright. All rights reserved.
Published: 2019

26. Correction of vasopressin deficit in the lateral septum ameliorates social deficits of mouse autism model

Author: Gilles Guillon, Amélie M. Borie, Michel G. Desarménien, Aleksandra Olma, Françoise Muscatelli, Maurice Manning, Freddy Jeanneteau, Yann Dromard, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Toledo, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Muscatelli, Françoise, Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
Subjects: Male, 0301 basic medicine, Vasopressin, Vasopressins, [SDV]Life Sciences [q-bio], Stimulation, Disease, Optogenetics, Mouse models, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigens, Neoplasm, Animals, Humans, Medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Autistic Disorder, Habituation, Social Behavior, Neuroendocrine regulation, Mice, Knockout, Neurons, Behavior, Animal, business.industry, Proteins, General Medicine, medicine.disease, Pathophysiology, [SDV] Life Sciences [q-bio], Disease Models, Animal, 030104 developmental biology, Somatostatin, 030220 oncology & carcinogenesis, Psychiatric diseases, Autism, Septal Nuclei, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Neuroscience, hormones, hormone substitutes, and hormone antagonists, Research Article
Abstract: International audience; Intellectual and social disabilities are common comorbidities in adolescents and adults with MAGE family member L2 (MAGEL2) gene deficiency characterizing the Prader-Willi and Schaaf-Yang neurodevelopmental syndromes. The cellular and molecular mechanisms underlying the risk for autism in these syndromes are not understood. We asked whether vasopressin functions are altered by MAGEL2 deficiency and whether a treatment with vasopressin could alleviate the disabilities of social behavior. We used Magel2-knockout mice (adult males) combined with optogenetic or pharmacological tools to characterize disease modifications in the vasopressinergic brain system and monitor its impact on neurophysiological and behavioral functions. We found that the activation of vasopressin neurons and projections in the lateral septum were inappropriate for performing a social habituation/discrimination task. Mechanistically, the lack of vasopressin impeded the deactivation of somatostatin neurons in the lateral septum, which predicted social discrimination deficits. Correction of vasopressin septal content by administration or optogenetic stimulation of projecting axons suppressed the activity of somatostatin neurons and ameliorated social behavior. This preclinical study identified vasopressin in the lateral septum as a key factor in the pathophysiology of Magel2-related neurodevelopmental syndromes.
Published: 2021

27. Content, diagnostic, correlational, and genetic similarities between common measures of childhood aggressive behaviors and related psychiatric traits

Author: Michel G. Nivard, Catharina E. M. van Beijsterveldt, Anne M. Hendriks, Catrin Finkenauer, Dorret I. Boomsma, Meike Bartels, Hill F. Ip, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, APH - Methodology, Leerstoel Finkenauer, and Youth in Changing Cultural Contexts
Subjects: Male, Netherlands Twin Register (NTR), clinical concordance, item overlap, Concordance, Twins, Childhoodaggressive behavior, Child Behavior, Mothers, Poison control, CBCL, Genetic correlation, Correlation, Fathers, 03 medical and health sciences, 0302 clinical medicine, Injury prevention, Developmental and Educational Psychology, Humans, 0501 psychology and cognitive sciences, Child, Child Psychiatry, Childhood aggressive behavior, 05 social sciences, Human factors and ergonomics, Original Articles, Child development, genetic correlation, Aggression, Psychiatry and Mental health, Phenotype, Pediatrics, Perinatology and Child Health, Original Article, Female, Psychology, 030217 neurology & neurosurgery, 050104 developmental & child psychology, Clinical psychology
Abstract: BACKGROUND: Given the role of childhood aggressive behavior (AGG) in everyday child development, precise and accurate measurement is critical in clinical practice and research. This study aims to quantify agreement among widely used measures of childhood AGG regarding item content, clinical concordance, correlation, and underlying genetic construct.METHODS: We analyzed data from 1254 Dutch twin pairs (age 8-10 years, 51.1% boys) from a general population sample for whom both parents completed the A-TAC, CBCL, and SDQ at the same occasion.RESULTS: There was substantial variation in item content among AGG measures, ranging from .00 (i.e., mutually exclusive) to .50 (moderate agreement). Clinical concordance (i.e., do the same children score above a clinical threshold among AGG measures) was very weak to moderate with estimates ranging between .01 and .43 for mother-reports and between .12 and .42 for father-reports. Correlations among scales were weak to strong, ranging from .32 to .70 for mother-reports and from .32 to .64 for father-reports. We found weak to very strong genetic correlations among the measures, with estimates between .65 and .84 for mother-reports and between .30 and .87 for father-reports.CONCLUSIONS: Our results demonstrated that degree of agreement between measures of AGG depends on the type (i.e., item content, clinical concordance, correlation, genetic correlation) of agreement considered. Because agreement was higher for correlations compared to clinical concordance (i.e., above or below a clinical cutoff), we propose the use of continuous scores to assess AGG, especially for combining data with different measures. Although item content can be different and agreement among observed measures may not be high, the genetic correlations indicate that the underlying genetic liability for childhood AGG is consistent across measures.
Published: 2020

28. Modulation of α

Author: Federica, Ciregia, Céline, Deroyer, Gaël, Cobraiville, Zelda, Plener, Olivier, Malaise, Philippe, Gillet, Marianne, Fillet, Michel G, Malaise, and Dominique, de Seny
Subjects: Male, Proteomics, Integrins, Synovitis, Middle Aged, Immunohistochemistry, Synoviocytes, Article, Immunophenotyping, Transforming Growth Factor beta1, Antigens, Neoplasm, Tandem Mass Spectrometry, Osteoarthritis, Humans, Female, Protein Interaction Domains and Motifs, Disease Susceptibility, Vitronectin, Cell culture, Inflammation Mediators, Peptides, Biomarkers, Aged, Chromatography, Liquid, Protein Binding
Abstract: Osteoarthritis is characterized by structural alteration of joints. Fibrosis of the synovial tissue is often detected and considered one of the main causes of joint stiffness and pain. In our earlier proteomic study, increased levels of vitronectin (VTN) fragment (amino acids 381–397) were observed in the serum of osteoarthritis patients. In this work, the affinity of this fragment for integrins and its putative role in TGF-β1 activation were investigated. A competition study determined the interaction of VTN(381–397 a.a.) with αVβ6 integrin. Subsequently, the presence of αVβ6 integrin was substantiated on primary human fibroblast-like synoviocytes (FLSs) by western blot and flow cytometry. By immunohistochemistry, β6 was detected in synovial membranes, and its expression showed a correlation with tissue fibrosis. Moreover, β6 expression was increased under TGF-β1 stimulation; hence, a TGF-β bioassay was applied. We observed that αVβ6 could mediate TGF-β1 bioavailability and that VTN(381–397 a.a.) could prevent TGF-β1 activation by interacting with αVβ6 in human FLSs and increased α-SMA. Finally, we analyzed serum samples from healthy controls and patients with osteoarthritis and other rheumatic diseases by nano-LC/Chip MS–MS, confirming the increased expression of VTN(381–397 a.a.) in osteoarthritis as well as in lupus erythematosus and systemic sclerosis. These findings corroborate our previous observations concerning the overexpression of VTN(381–397 a.a.) in osteoarthritis but also in other rheumatic diseases. This fragment interacts with αVβ6 integrin, a receptor whose expression is increased in FLSs from the osteoarthritic synovial membrane and that can mediate the activation of the TGF-β1 precursor in human FLSs., Rheumatology: A starting point for joint disease Insights into a mechanism underlying the formation of fibrotic tissue within joints in osteoarthritis may also prove relevant to other rheumatological disorders. The general mechanisms underlying fibrosis are reasonably well understood, but it remains unclear what triggers these processes in osteoarthitis. Researchers of the University of Liège in Belgium have uncovered a possible explanation based on experiments with cultured primary synovial fibroblasts from patients. Osteoarthitis is characterized by increased levels of a fragment of the protein vitronectin, and the researchers demonstrated that this in turn binds to a protein called αVβ6, potentially promoting initiation of fibrosis. They also observed elevated levels of the same vitronectin fragment in two other rheumatoid disorders, lupus and systemic sclerosis, and concluded that further research is needed to characterize this protein’s role in inflammation and fibrosis.
Published: 2020

29. Electrical storm in patients with left ventricular assist devices: Risk factors, incidence, and impact on survival

Author: Jonathan P. Piccini, Chetan B. Patel, Jacob N. Schroder, Sounok Sen, Carmelo A. Milano, Daniel J. Friedman, Michael Rehorn, Michel G. Khouri, Eric Black-Maier, Sean D. Pokorney, Jason I. Koontz, James P. Daubert, Jason N. Katz, Albert Y. Sun, and Rahul S. Loungani
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Heart Ventricles, Population, Catheter ablation, 030204 cardiovascular system & hematology, Ventricular tachycardia, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Risk Factors, Physiology (medical), Internal medicine, medicine, Humans, 030212 general & internal medicine, education, Aged, Retrospective Studies, Heart Failure, education.field_of_study, business.industry, Incidence, Retrospective cohort study, Perioperative, Middle Aged, medicine.disease, United States, Survival Rate, Heart failure, Ventricular assist device, Cardiology, Tachycardia, Ventricular, Equipment Failure, Female, Heart-Assist Devices, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Background Ventricular arrhythmias (VAs) and electrical storm (ES) are recognized complications following left ventricular assist device (LVAD) implantation; however, their association with long term-outcomes remains poorly understood. Objective The purpose of this study was to describe the clinical impact of ES in a population of patients undergoing LVAD implantation at a quaternary care center in the United States. Methods This was an observational retrospective study of patients undergoing LVAD implantation from 2009 to 2020 at Duke University Hospital. The incidence of ES (≥3 sustained VA episodes over a 24-hour period without an identifiable reversible cause) was determined from patient records. Risk factors for ES were identified using multivariable Cox proportional hazards modeling. Results Among 730 patients undergoing LVAD implant, 78 (10.7%) developed ES at a median of 269 (interquartile range [IQR] 7–766) days following surgery. Twenty-seven patients (34.6%) developed ES within 30 days, while 51 (65.4%) presented with ES at a median 639 (IQR 281–1017) days after implant. Following ES, 41% of patients died within 1 year. Patients who developed ES were more likely to have a history of VAs, ventricular tachycardia ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support around the time of LVAD implant than patients without ES. Conclusion ES occurs in 1 in 10 patients after LVAD and is associated with higher mortality. Risk factors for ES include a history of VAs, VT ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support. Optimal management of ES surrounding LVAD implant, including escalation of medical therapy, catheter ablation, or adjunctive sympatholytic therapies, remains uncertain.
Published: 2020

30. Catheter ablation of atrial fibrillation in cardiac amyloidosis

Author: Jonathan P. Piccini, Rahul S. Loungani, Fawaz Alenezi, Michael Rehorn, James P. Daubert, Kevin L. Thomas, Sean D. Pokorney, Albert Y. Sun, Kyle R. Geurink, Kevin P. Jackson, Daniel J. Friedman, Brett D. Atwater, Tristram D. Bahnson, Eric Black-Maier, Michel G. Khouri, and Donald D. Hegland
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Catheter ablation, 030204 cardiovascular system & hematology, 03 medical and health sciences, Electrocardiography, 0302 clinical medicine, Recurrence, Internal medicine, Atrial Fibrillation, medicine, Humans, 030212 general & internal medicine, Atrial tachycardia, Aged, Retrospective Studies, Ejection fraction, business.industry, Atrial fibrillation, General Medicine, Amyloidosis, medicine.disease, Ablation, Cardiac amyloidosis, Echocardiography, cardiovascular system, Cardiology, Catheter Ablation, Female, medicine.symptom, Electrical conduction system of the heart, Cardiology and Cardiovascular Medicine, business, Cardiomyopathies, Atrial flutter
Abstract: Background: Cardiac amyloidosis is a progressive infiltrative disease involving deposition of amyloid fibrils in the myocardium and cardiac conduction system that frequently manifests with heart failure (HF) and arrhythmias, most frequently atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). Methods: We performed an observational retrospective study of patients with a diagnosis of cardiac amyloid who underwent catheter ablation at our institution between January 1, 2011 and December 1, 2018. Patient demographics, procedural characteristics and outcomes were determined by manual chart review. Results: A total of 13 catheter ablations were performed over the study period in patients with cardiac amyloidosis, including 10 AT/AF/AFL ablations and 3 atrioventricular nodal ablations. Left ventricular ejection fraction was lower at the time of AV node ablation than catheter ablation of AT/AF/AFL (23% vs. 40%, p = 0.003). Cardiac amyloid was diagnosed based on the results of pre-ablation cardiac MRI results in the majority of patients (n = 7, 70%). The HV interval was prolonged at 60±15 ms and did not differ significantly between AV nodal ablation patients and AT/AF/AFL ablation patients (69±18 ms vs. 57±14 ms, p = 0.36). The majority of patients undergoing AT/AF/AFL ablation had persistent AF (n = 7, 70%) and NYHA class II (n = 5, 50%) or III (n = 5, 50%) HF symptoms, while patients undergoing AV node ablation were more likely to have class IV HF (n = 2, 66%, p = 0.014). Arrhythmia-free survival in CA patients after catheter ablation of AT/AF/AFL was 40% at one year and 20% at two years. Conclusions: Catheter ablation of AT/AF/AFL may be a feasible strategy for appropriately selected patients with early to mid-stage CA, whereas AV node ablation may be more appropriate in patients with advanced stage CA. This article is protected by copyright. All rights reserved.
Published: 2020

31. Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Author: Coleman, Jonathan RI, Peyrot, Wouter J, Purves, Kirstin L, Davis, Katrina AS, Rayner, Christopher, Choi, Shing Wan, Hubel, Christopher, Gaspar, Helena A, Kan, Carol, Van der Auwera, Sandra, Adams, Mark James, Lyall, Donald M, Choi, Karmel W, Dunn, Erin C, Vassos, Evangelos, Danese, Andrea, Maughan, Barbara, Grabe, Hans J, Lewis, Cathryn M, O'Reilly, Paul F, McIntosh, Andrew M, Smith, Daniel J, Wray, Naomi R, Hotopf, Matthew, Eley, Thalia C, Breen, Gerome, Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M, Abdellaoui, Abdel, Adams, Mark J, Agerbo, Esben, Air, Tracy M, Andlauer, Till FM, Bacanu, Silviu-Alin, Baekvad-Hansen, Marie, Beekman, Aartjan TF, Bigdeli, Tim B, Binder, Elisabeth B, Bryois, Julien, Buttenschon, Henriette N, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Colodro-Conde, Lucia, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Deary, Ian J, Degenhardt, Franziska, Derks, Eske M, Direk, Nese, Dolan, Conor V, Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K, Foo, Jerome C, Forstner, Andreas J, Frank, Josef, Gill, Michael, Goes, Fernando S, Gordon, Scott D, Grove, Jakob, Hall, Lynsey S, Hansen, Christine Soholm, Hansen, Thomas F, Herms, Stefan, Hickie, Ian B, Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M, Howard, David M, Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A, Jorgenson, Eric, Knowles, James A, Kohane, Isaac S, Kraft, Julia, Kretzschmar, Warren W, Kutalik, Zoltan, Li, Yihan, Lind, Penelope A, MacIntyre, Donald J, MacKinnon, Dean F, Maier, Robert M, Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M, Montgomery, Grant W, Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, Oskarsson, Hogni, Owen, Michael J, Painter, Jodie N, Pedersen, Carsten Bocker, Pedersen, Marianne Giortz, Peterson, Roseann E, Pettersson, Erik, Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A, Qvist, Per, Rice, John P, Riley, Brien P, Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Shi, Jianxin, Shyn, Stanley I, Sigurdsson, Engilbert, Sinnamon, Grant CB, Smit, Johannes H, Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Thorgeirsson, Thorgeir E, Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andres G, Umbricht, Daniel, van Hemert, Albert M, Viktorin, Alexander, Visscher, Peter M, Wang, Yunpeng, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jurgen, Willemsen, Gonneke, Witt, Stephanie H, Wu, Yang, Xi, Hualin S, Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T, Berger, Klaus, Boomsma, Dorret I, Cichon, Sven, Dannlowski, Udo, de Geus, EJC, DePaulo, J Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tonu, Hamilton, Steven P, Hayward, Caroline, Heath, Andrew C, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S, Lucae, Susanne, Madden, Pamela AF, Magnusson, Patrik K, Martin, Nicholas G, Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Mueller-Myhsok, Bertram, Nordentoft, Merete, Noethen, Markus M, O'Donovan, Michael C, Paciga, Sara A, Pedersen, Nancy L, Penninx, Brenda WJH, Perlis, Roy H, Porteous, David J, Potash, James B, Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G, Smoller, Jordan W, Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Volzke, Henry, Weissman, Myrna M, Werge, Thomas, Levinson, Douglas F, Borglum, Anders D, Sullivan, Patrick F, Consortium, Psychiat Genomics, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Methodology, APH - Digital Health, Adult Psychiatry, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Sociology and Social Gerontology, Complex Trait Genetics, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), on the behalf of Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T.M., Andlauer, TFM, Bacanu, S.A., Bækvad-Hansen, M., Beekman, ATF, Bigdeli, T.B., Binder, E.B., Bryois, J., Buttenschøn, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J.H., Clarke, T.K., Coleman, JRI, Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Kiadeh, FFH, Finucane, H.K., Foo, J.C., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Howard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., Jorgenson, E., Knowles, J.A., Kohane, I.S., Kraft, J., Kretzschmar, W.W., Kutalik, Z., Li, Y., Lind, P.A., MacIntyre, D.J., MacKinnon, D.F., Maier, R.M., Maier, W., Marchini, J., Mbarek, H., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J., Shyn, S.I., Sigurdsson, E., Sinnamon, GCB, Smit, J.H., Smith, D.J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K.E., Teismann, H., Teumer, A., Thompson, W., Thomson, P.A., Thorgeirsson, T.E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A.G., Umbricht, D., Van der Auwera, S., van Hemert, A.M., Viktorin, A., Visscher, P.M., Wang, Y., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.S., Yang, J., Zhang, F., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., de Geus, EJC, DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.S., Lucae, S., Madden, PAF, Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Müller-Myhsok, B., Nordentoft, M., Nöthen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, BWJH, Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Völzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Børglum, A.D., and Sullivan, P.F.
Subjects: Netherlands Twin Register (NTR), 0301 basic medicine, Male, SYMPTOMS, Databases, Factual, Genome-wide association study, 0302 clinical medicine, Medicine, Depression (differential diagnoses), RISK, HERITABILITY, PSYCHIATRIC-DISORDERS, Middle Aged, Psychiatry and Mental health, Major depressive disorder, Female, Waist Circumference, MENTAL-HEALTH, Psychological trauma, Clinical psychology, Adult, Psychological Trauma, Genetic correlation, CHILDHOOD MALTREATMENT, Article, EVENTS, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, ADVERSITY, mental disorders, SNP, Humans, Genetic Predisposition to Disease, Molecular Biology, Genetic association, Aged, Depressive Disorder, Major, business.industry, Heritability, medicine.disease, United Kingdom, ASSOCIATION ANALYSIS, 030104 developmental biology, BIOLOGICAL INSIGHTS, Gene-Environment Interaction, Self Report, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (r g = 0.24, p = 1.8 × 10 -7 versus r g = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10 -4 ). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.
Published: 2020

32. Cardiac Implantable Electronic Devices: A Window Into the Evolution of Conduction Disease in Cardiac Amyloidosis

Author: Michael R, Rehorn, Rahul S, Loungani, Eric, Black-Maier, Amanda C, Coniglio, Ravi, Karra, Sean D, Pokorney, and Michel G, Khouri
Subjects: Male, Amyloid Neuropathies, Familial, Cardiac Conduction System Disease, Humans, Arrhythmias, Cardiac, Female, Electronics, Aged, Defibrillators, Implantable
Abstract: This study characterized the relationship between conduction disease and cardiac amyloidosis (CA) through longitudinal analysis of cardiac implantable electronic device (CIED) data.Bradyarrhythmias and tachyarrhythmias are commonly reported in CA and may precede a CA diagnosis, although the natural history of conduction disease in CA is not well-described.Patients with CA (transthyretin amyloidosis cardiomyopathy [ATTR-CM] and light-chain amyloidosis [AL-CA]) and a CIED were identified within the Duke University Health System. Patient characteristics at the time of implantation, including demographics and data relevant to CA diagnosis, cardiac imaging, and CIED were recorded. CIED interrogations were analyzed for pacing and atrial fibrillation (AF) burden, activity level, lead parameters, and ventricular arrhythmia incidence and/or therapy.Thirty-four patients with CA (7 with AL-CA, 27 with ATTR-CM [78% with wild-type]; 82% men) with median age of 75 years and a mean ejection fraction of 42 ± 13% had a CIED implanted for bradycardia (65%) or prevention of sudden cardiac death (35%). CIED implantation preceded CA diagnosis in 14 patients (41%). Over a mean follow-up of 3.1 ± 4.0 years, right ventricular sensing amplitudes decreased but did not result in device malfunction; lead impedances and capture thresholds remained stable. Between post-implantation years 1 and 5, mean ventricular pacing increased from 56 ± 9% to 96 ± 1% (p = 0.003) and AF burden increased from 2 ± 1.3 to 17 ± 3 h/day (p = 0.0002). Ventricular arrhythmias were common (mean episodes per patient per year: 6.7 ± 2.3 [ATTR-CM] and 5.1 ± 3.2 [AL-CA]) but predominately nonsustained; only 1 patient with AL-CA required implantable cardioverter-defibrillator therapy.Longitudinal analysis of CIED data in patients with CA revealed progressive conduction disease, with high AF burden and eventual dependence on ventricular pacing, although lead parameters remained stable. Ventricular arrhythmias were common but predominantly nonsustained, particularly in ATTR-CM.
Published: 2020

33. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Author: Shen, Xueyi, Howard, David M, McIntosh, Andrew M, O'Reilly, Paul F, Oskarsson, Hogni, Owen, Michael J, Painter, Jodie N, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E, Pettersson, Erik, Peyrot, Wouter J, Pistis, Giorgio, Deary, Ian J, Posthuma, Danielle, Quiroz, Jorge A, Qvist, Per, Rice, John P, Riley, Brien P, Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Wray, Naomi R, Shi, Jianxin, Shyn, Stanley I, Sigurdsson, Engilbert, Sinnamon, Grant C B, Smit, Johannes H, Smith, Daniel J, Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Ripke, Stephan, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Thorgeirsson, Thorgeir E, Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andrés G, Mattheisen, Manuel, Umbricht, Daniel, Auwera, Sandra Van der, van Hemert, Albert M, Viktorin, Alexander, Visscher, Peter M, Wang, Yunpeng, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Trzaskowski, Maciej, Witt, Stephanie H, Wu, Yang, Xi, Hualin S, Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T, Berger, Klaus, Boomsma, Dorret I, Cichon, Sven, Byrne, Enda M, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J, Hamilton, Steven P, Hayward, Caroline, Heath, Andrew C, Abdellaoui, Abdel, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S, Lucae, Susanne, Madden, Pamela A F, Magnusson, Patrik K, Martin, Nicholas G, Metspalu, Andres, Mors, Ole, Agerbo, Esben, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M, O'Donovan, Michael C, Paciga, Sara A, Pedersen, Nancy L, Penninx, Brenda W J H, Perlis, Roy H, Porteous, David J, Air, Tracy M, Potash, James B, Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G, Smoller, Jordan W, Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Adams, Mark J, Andlauer, Till F M, Weissman, Myrna M, Werge, Thomas, Lewis, Cathryn M, Levinson, Douglas F, Breen, Gerome, Børglum, Anders D, Sullivan, Patrick F, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T F, Bigdeli, Tim B, Binder, Elisabeth B, Bryois, Julien, Buttenschøn, Henriette N, Bybjerg-Grauholm, Jonas, Cai, Na, Hill, W David, Castelao, Enrique, Christensen, Jane Hvarregaard, Coleman, Jonathan R I, Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Degenhardt, Franziska, Derks, Eske M, Clarke, Toni-Kim, Direk, Nese, Dolan, Conor V, Dunn, Erin C, Eley, Thalia C, Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K, Foo, Jerome C, Forstner, Andreas J, Frank, Josef, Gaspar, Héléna A, Gill, Michael, Goes, Fernando S, Gordon, Scott D, Grove, Jakob, Hall, Lynsey S, Hansen, Christine Søholm, Hansen, Thomas F, Herms, Stefan, Hickie, Ian B, Whalley, Heather C, Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M, Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A, Jorgenson, Eric, Knowles, James A, Kohane, Isaac S, Kraft, Julia, Kretzschmar, Warren W, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A, MacIntyre, Donald J, MacKinnon, Dean F, Maier, Robert M, Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M, Montgomery, Grant W, Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, Human genetics, APH - Methodology, Epidemiology and Data Science, APH - Digital Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Adult Psychiatry, Shen, Xueyi [0000-0002-0538-4774], Howard, David M [0000-0002-6005-1972], Adams, Mark J [0000-0002-3599-6018], Whalley, Heather C [0000-0002-4505-8869], McIntosh, Andrew M [0000-0002-0198-4588], Apollo - University of Cambridge Repository, Epidemiology, Erasmus MC other, Urology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Medical Informatics, Immunology, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), DISORDER, Male, General Physics and Astronomy, Genome-wide association study, Genome-wide association studies, 0302 clinical medicine, Risk Factors, SCHIZOPHRENIA, Medicine, lcsh:Science, Depression (differential diagnoses), Biological Specimen Banks, Multidisciplinary, Depression, Phenome-wide association, Mendelian Randomization Analysis, Middle Aged, Biobank, 3. Good health, ENVIRONMENT INTERACTION, symbols, Female, ddc:500, Clinical psychology, Science, Prefrontal Cortex, Genomics, Neuroimaging, Phenome, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, symbols.namesake, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, Mendelian Randomisation, Þunglyndi, Aged, business.industry, General Chemistry, MAJOR DEPRESSION, Mental health, Genarannsóknir, 030104 developmental biology, Mendelian inheritance, lcsh:Q, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Publisher's version (útgefin grein), Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR, The present study is supported by a Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (STRADL) (Reference 104036/Z/14/Z) and MRC Mental Health Data Pathfinder Award (Reference MC_PC_17209). Data acquisition and analyses were conducted using the UK Biobank Resource under approved project #4844. Participation of the UK Biobank subjects is gratefully appreciated. We also thank UK Biobank team for collecting and preparing data for analyses. Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. The PGC has received major funding from the US National Institute of Mental Health (5 U01MH109528-03). We thank the research participants and employees of 23andMe for supporting this study. X.S. receives support from China Scholarship Council (No. 201506040037). H.C.W. is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. D.M.H. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Reference 213674/Z/18/Z) and a 2018 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Reference 27404). W.D.H. is supported by a grant from Age UK (Disconnected Mind Project). A.M.M. is supported by the Sackler Trust. I.J.D. is a participant in UK Biobank.
Published: 2020

34. A role for vitamin D and omega-3 fatty acids in major depression? An exploration using genomics

Author: Wouter J. Peyrot, Yuri Milaneschi, Brenda W. J. H. Penninx, Dorret I. Boomsma, Hamdi Mbarek, Michel G. Nivard, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Digital Health, Biological Psychology, and APH - Methodology
Subjects: Adult, Male, 0301 basic medicine, Netherlands Twin Register (NTR), Multifactorial Inheritance, Context (language use), Genome-wide association study, Bioinformatics, Article, lcsh:RC321-571, Cellular and Molecular Neuroscience, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Fatty Acids, Omega-3, Mendelian randomization, Vitamin D and neurology, Humans, Medicine, Vitamin D, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, 030304 developmental biology, Genetic association, Depressive Disorder, Major, 0303 health sciences, Depression, business.industry, Confounding, Genomics, Middle Aged, medicine.disease, 3. Good health, Psychiatry and Mental health, 030104 developmental biology, Mood, Pharmacogenetics, Major depressive disorder, Female, Observational study, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: BackgroundTrials testing the effect of vitamin D or omega-3 fatty acids (n3-PUFA) supplementation on major depressive disorder (MDD) reported conflicting findings. These trials were boosted by epidemiological evidence suggesting an inverse association of circulating 25-hydroxyvitamin D (25-OH-D) and n3-PUFA levels with MDD. Observational associations may emerge from unresolved confounding, shared genetic risk, or direct causal relationships. We explored the nature of these associations exploiting data and statistical tools from genomics.MethodsResults from GWAS on 25-OH-D (N = 79366), n3-PUFA (N = 24925) and MDD (135458 cases, 344901 controls) were applied to individual-level data (>2,000 subjects with measures of genotype, DSM-IV lifetime MDD diagnoses and circulating 25-OH-D and n3-PUFA) and summary-level data analyses. Shared genetic risk between traits was tested by polygenic risk scores (PRS). Two-sample Mendelian Randomization (2SMR) analyses tested the potential bidirectional causality between traits.OutcomeIn individual-level data, PRS were associated with the phenotype of the same trait (PRS 25-OH-D p = 1.4e-20, PRS N3-PUFA p = 9.3e-6, PRS MDD p = 1.4e-4), but not with the other phenotypes, suggesting a lack of shared genetic effects. In summary-level data, 2SMR analyses provided no evidence of a causal role on MDD of 25-OH-D (p = 0.50) or n3-PUFA (p = 0.16), or for a causal role of MDD on 25-OH-D (p = 0.25) or n3-PUFA (p = 0.66).ConclusionsApplying genomics tools indicated that that shared genetic risk or direct causality between 25-OH-D, n3-PUFA and MDD is unlikely: unresolved confounding may explain the associations reported in observational studies. These findings represent a cautionary tale for testing supplementation of these compounds in preventing or treating MDD.Research in contextEvidence before this studyMeta-analyses of trials testing the effect of vitamin D or omega-3 fatty acids (n3-PUFA) supplementation on major depressive disorder (MDD) reported conflicting findings, including small clinical effect or no effect. These trials were boosted by epidemiological evidence suggesting an inverse association of circulating 25-hydroxyvitamin D (25-OH-D) and n3-PUFA levels with MDD. However, observational associations may emerge from different scenarios, including unresolved confounding, shared genetic risk, or direct causal relationships.Added value of this studyGenomics provides unique opportunities to investigate shared risk and causality between traits applying new statistical tools and results from genome-wide association studies (GWAS). In the present study we examined the nature of the association of 25-OH-D and n3-PUFA with MDD using the latest data and tools from genomics. We found no significant evidence of shared genetic risk or direct causality between vitamin D or n-3 PUFA and MDD; at this stage, unresolved confounding should be considered the most likely explanation for the association reported by observational studies.Implications of all the available evidenceFindings from the present study, in conjunction with previous conflicting evidence from clinical studies, represent a cautionary tale for further research testing the potential therapeutic effect of vitamin D and n3-PUFA supplementation on depression, as the expectations of a direct causal effect of these compounds on mood should be substantially reconsidered. Genomic tools could be efficiently employed to examine the nature of observational associations emerging in epidemiology, providing some indications on the most promising associations to be prioritized in subsequent intervention studies.
Published: 2019

35. Does Childhood Trauma Moderate Polygenic Risk for Depression?

Author: Wouter J. Peyrot, Sandra Van der Auwera, Yuri Milaneschi, Conor V. Dolan, Pamela A.F. Madden, Patrick F. Sullivan, Jana Strohmaier, Stephan Ripke, Marcella Rietschel, Michel G. Nivard, Niamh Mullins, Grant W. Montgomery, Anjali K. Henders, Andrew C. Heat, Helen L. Fisher, Erin C. Dunn, Enda M. Byrne, Tracy A. Air, Bernhard T. Baune, Gerome Breen, Douglas F. Levinson, Cathryn M. Lewis, Nick G. Martin, Elliot N. Nelson, Dorret I. Boomsma, Hans J. Grabe, Naomi R. Wray, Brenda W.J.H. Penninx, Manuel Mattheisen, Maciej Trzaskowski, Abdel Abdellaoui, Mark J. Adams, Esben Agerbo, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Douglas H.R. Blackwood, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R.I. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Nese Direk, Thalia C. Eley, Valentina Escott-Price, null Farnush, Farhadi Hassan Kiadeh, Hilary K. Finucane, Andreas J. Forstner, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hicki, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Sara Mostafavi, Matthias Nauck, Bernard Ng, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Michael J. Owen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Erik Pettersson, Giorgio Pistis, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Jianxin Shi, Stanley I. Shyn, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Klaus Berger, Sven Cichon, Udo Dannlowski, E.J.C. de Geus, J. Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, Kenneth S. Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S. Li, Susanne Lucae, Patrik K. Magnusson, Nicholas G. Martin, Andrew M. McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M. Nöthen, Michael C. O'Donovan, Sara A. Paciga, Nancy L. Pedersen, Roy H. Perlis, David J. Porteous, James B. Potash, Martin Preisig, Catherine Schaefer, Thomas G. Schulze, Jordan W. Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M. Weissman, Thomas Werge, Anders D. Børglum, Biological Psychology, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Adult Psychiatry, ARD - Amsterdam Reproduction and Development, Epidemiology, Urology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Medical Informatics, Immunology, Psychiatry, Amsterdam Reproduction & Development (AR&D), Human genetics, Epidemiology and Data Science, and APH - Digital Health
Subjects: 0301 basic medicine, Child abuse, Adult, Male, Netherlands Twin Register (NTR), medicine.medical_specialty, Multifactorial Inheritance, polygenic risk, SDG 16 - Peace, interaction, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, mental disorders, medicine, Journal Article, Humans, genetics, Genetic Predisposition to Disease, Child Abuse, Psychiatry, Child, Biological Psychiatry, Psychiatric Status Rating Scales, Depressive Disorder, Major, childhood trauma, Genetic heterogeneity, Depression, Adult Survivors of Child Abuse, SDG 16 - Peace, Justice and Strong Institutions, Case-control study, Odds ratio, medicine.disease, Justice and Strong Institutions, meta-analysis, 030104 developmental biology, Physical abuse, Logistic Models, 5-HTTLPR, Meta-analysis, Case-Control Studies, Major depressive disorder, Female, Gene-Environment Interaction, Psychology, 030217 neurology & neurosurgery
Abstract: BackgroundThe heterogeneity of genetic effects on major depressive disorder (MDD) may be partly attributable to moderation of genetic effects by environment, such as exposure to childhood trauma (CT). Indeed, previous findings in two independent cohorts showed evidence for interaction between polygenic risk scores (PRSs) and CT, albeit in opposing directions. This study aims to meta-analyze MDD-PRS × CT interaction results across these two and other cohorts, while applying more accurate PRSs based on a larger discovery sample.MethodsData were combined from 3024 MDD cases and 2741 control subjects from nine cohorts contributing to the MDD Working Group of the Psychiatric Genomics Consortium. MDD-PRS were based on a discovery sample of ∼110,000 independent individuals. CT was assessed as exposure to sexual or physical abuse during childhood. In a subset of 1957 cases and 2002 control subjects, a more detailed five-domain measure additionally included emotional abuse, physical neglect, and emotional neglect.ResultsMDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 × 10-5, R2 = 1.18%) and with CT (OR = 2.63, p = 3.5 × 10-18 and OR = 2.62, p = 1.4 ×10-5 for the two- and five-domain measures, respectively). No interaction was found between MDD-PRS and the two-domain and five-domain CT measure (OR = 1.00, p = .89 and OR = 1.05, p = .66).ConclusionsNo meta-analytic evidence for interaction between MDD-PRS and CT was found. This suggests that the previously reported interaction effects, although both statistically significant, can best be interpreted as chance findings. Further research is required, but this study suggests that the genetic heterogeneity of MDD is not attributable to genome-wide moderation of genetic effects by CT.
Published: 2018

36. Association Between Population Density and Genetic Risk for Schizophrenia

Author: Lucía Colodro-Conde, Jian Yang, Dorret I. Boomsma, David C. Whiteman, Marjolijn Das, Baptiste Couvy-Duchesne, Rachel E. Neale, Sarah E. Medland, Catherine M. Olsen, Fabian Streit, Scott Gordon, Loic Yengo, Nicholas G. Martin, Maciej Trzaskowski, Marcella Rietschel, Stuart MacGregor, Michel G. Nivard, John J. McGrath, Kathryn E. Kemper, John Whitfield, Eveline L. de Zeeuw, Zhili Zheng, Department of Technology and Operations Management, Oral and Maxillofacial Surgery, Sociology, Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Methodology, and APH - Mental Health
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), DISORDER, Multifactorial Inheritance, Genome-wide association study, PRS, FAMILY-HISTORY, 0302 clinical medicine, Residence Characteristics, Risk Factors, Medicine, Family history, SOCIAL STRESS, Netherlands, Original Investigation, URBANIZATION, Middle Aged, Psychiatry and Mental health, ALCOHOL DEPENDENCE RISK, LIABILITY, Schizophrenia, Female, Adult, URBANICITY, BIRTH, Lower risk, Risk Assessment, 03 medical and health sciences, PSYCHOSIS, Mendelian randomization, Humans, Genetic Predisposition to Disease, Socioeconomic status, METAANALYSIS, Genetic association, Aged, Population Density, business.industry, Australia, Mendelian Randomization Analysis, medicine.disease, United Kingdom, 030104 developmental biology, Social Class, Residence, Gene-Environment Interaction, business, 030217 neurology & neurosurgery, Demography, Genome-Wide Association Study
Abstract: Importance: Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas.Objective: To assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk.Design, Setting, and Participants: Four large, cross-sectional samples of genotyped individuals of European ancestry older than 18 years with known addresses in Australia, the United Kingdom, and the Netherlands were included in the analysis. Data were based on the postcode of residence at the time of last contact with the participants. Community-based samples who took part in studies conducted by the Queensland Institute for Medical Research Berghofer Medical Research Institute (QIMR), UK Biobank (UKB), Netherlands Twin Register (NTR), or QSkin Sun and Health Study (QSKIN) were included. Genome-wide association analysis and mendelian randomization (MR) were included. The study was conducted between 2016 and 2018.Exposures: Polygenic risk scores for schizophrenia derived from genetic data (genetic risk is independently measured from the occurrence of the disease). Socioeconomic status of the area was included as a moderator in some of the models.Main Outcomes and Measures: Population density of the place of residence of the participants determined from census data. Remoteness and socioeconomic status of the area were also tested.Results: The QIMR participants (15 544; 10 197 [65.6%] women; mean [SD] age, 54.4 [13.2] years) living in more densely populated areas (people per square kilometer) had a higher genetic loading for schizophrenia (r2 = 0.12%; P = 5.69 × 10-5), a result that was replicated across all 3 other cohorts (UKB: 345 246; 187 469 [54.3%] women; age, 65.7 [8.0] years; NTR: 11 212; 6727 [60.0%] women; age, 48.6 [17.5] years; and QSKIN: 15 726; 8602 [54.7%] women; age, 57.0 [7.9] years). This genetic association could account for 1.7% (95% CI, 0.8%-3.2%) of the schizophrenia risk. Estimates from MR analyses performed in the UKB sample were significant (b = 0.049; P = 3.7 × 10-7 using GSMR), suggesting that the genetic liability to schizophrenia may have a causal association with the tendency to live in urbanized locations.Conclusions and Relevance: The results of this study appear to support the hypothesis that individuals with increased genetic risk tend to live in urban/dense areas and suggest the need to refine the social stress model for schizophrenia by including genetics as well as possible gene-environment interactions.
Published: 2018

37. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

Author: Jens Treutlein, James B. Potash, Cheynna A. Crowley, Paul F. O'Reilly, Francis M. Mondimore, Nicholas G. Martin, Jodie N. Painter, Qingqin S. Li, Tõnu Esko, Michael Conlon O'Donovan, Markus M. Nöthen, Toni-Kim Clarke, Roseann E. Peterson, Shantel Weinsheimer, Naomi R. Wray, Marie Bækvad-Hansen, Pamela F.A. Madden, Johannes H. Smit, Gonneke Willemsen, Thomas Hansen, Andrew C. Heath, Carsten Horn, Udo Dannlowski, Fulai Jin, Robert A. Schoevers, Jian Yang, Nicholas Eriksson, Marianne Giørtz Pedersen, Patrik K. E. Magnusson, Hans J. Grabe, Michael Gill, Lili Milani, Caroline Hayward, Shaun Purcell, Stanley I. Shyn, Penelope A. Lind, Giorgio Pistis, Michel G. Nivard, Thorgeir E. Thorgeirsson, Abdel Abdellaoui, Andres Metspalu, David J. Porteous, Anders D. Børglum, Christine Søholm Hansen, Scott D. Gordon, Nicholas John Craddock, Susanne Lucae, Douglas Blackwood, Jürgen Wellmann, Till M.F. Andlauer, Wesley K. Thompson, Chao Tian, Rudolf Uher, Nese Direk, Yuri Milaneschi, Paola Giusti-Rodríguez, Rick Jansen, Marcus Ising, Yang Wu, Jesper Krogh, Merete Nordentoft, Jouke-Jan Hottenga, Robert Maier, Ming Hu, Kari Stefansson, Glyn Lewis, Peter McGuffin, Wolfgang Maier, Erin C. Dunn, Bradley T. Webb, Gerome Breen, Henning Teismann, Eric Jorgenson, Jorge A. Quiroz, Brenda W.J.H. Penninx, Jonas Bybjerg-Grauholm, Warren W. Kretzschmar, Dean F. MacKinnon, Craig A. Stockmeier, Wouter J. Peyrot, Enrico Domenici, E. C.J. De Geus, Alexander Teumer, Henry Völzke, Yihan Li, Michael John Owen, Manuel Mattheisen, Bernard Ng, Baptiste Couvy-Duchesne, Daniel J. Smith, Jana Strohmaier, Vassily Trubetskoy, Volker Arolt, Douglas F. Levinson, Futao Zhang, Daniel Umbricht, Aartjan F.T. Beekman, David A. Hinds, Bernhard T. Baune, Henning Tiemeier, Hualin S. Xi, Hamdi Mbarek, Steven P. Hamilton, Stefan Kloiber, Fernando S. Goes, Jianxin Shi, Marcella Rietschel, Dale R. Nyholt, Zoltán Kutalik, Niamh Mullins, Grant W. Montgomery, Henriette N. Buttenschøn, Georg Homuth, Katharina Domschke, Alexander Viktorin, Hilary K. Finucane, Ashley R. Winslow, Saira Saeed Mirza, Fabian Streit, Erik Pettersson, Martin Preisig, Danielle Posthuma, Stephan Ripke, Lucía Colodro-Conde, Thalia C. Eley, Pippa A. Thomson, Thomas Werge, Enrique Castelao, Klaus Berger, Yun Li, Stacy Steinberg, Dorret I. Boomsma, Matthias Nauck, Sara Mostafavi, Jacqueline M. Lane, Katherine E. Tansey, Divya Mehta, Gregory E. Crawford, Andreas J. Forstner, Jane H. Christensen, Silviu Alin Bacanu, Julia Kraft, David M. Hougaard, Peter M. Visscher, Valentina Escott-Price, Donald J. MacIntyre, Sarah E. Medland, Per Qvist, Kenneth S. Kendler, Jordan W. Smoller, J. Raymond DePaulo, Ian J. Deary, Thomas G. Schulze, Julien Bryois, Ian B. Hickie, Helena Gaspar, Jonathan Mill, James A. Knowles, Cathryn M. Lewis, Hassan S. Dashti, Stefan Herms, Margarita Rivera, John P. Rice, Lynsey S. Hall, Eilis Hannon, Nancy L. Pedersen, Eva C. Schulte, Hreinn Stefansson, Maciej Trzaskowski, André G. Uitterlinden, Bertram Müller-Myhsok, Gail Davies, Mark Adams, Jakob Grove, Eske M. Derks, Sven Cichon, Jonathan I.R. Coleman, Sandra Van der Auwera, Myrna M. Weissman, Preben Bo Mortensen, Josef Frank, Enda M. Byrne, Esben Agerbo, Engilbert Sigurdsson, Xiaoxiao Liu, Patrick F. Sullivan, Carsten Bøcker Pedersen, Ole Mors, Catherine Schaefer, Richa Saxena, Albert M. van Hemert, Jonathan Marchini, Hogni Oskarsson, Franziska Degenhardt, Tracy Air, Elisabeth B. Binder, Christel M. Middeldorp, Farnush Hassan Farhadi Kiadeh, Conor V. Dolan, Sara A. Paciga, Per Hoffmann, Leina Lu, Andrew M. McIntosh, Tim B. Bigdeli, Stephanie H. Witt, Matthew Traylor, Grant Sinnamon, Brien P. Riley, Roy H. Perlis, Patrick J. McGrath, Craig L. Hyde, Ling Shen, Na Cai, Yunpeng Wang, Evelin Mihailov, Isaac S. Kohane, APH - Mental Health, Adult Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Integrative Neurophysiology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, Amsterdam Reproduction & Development (AR&D), Human genetics, Epidemiology and Data Science, APH - Digital Health, Epidemiology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, eQTLGen, 23andMe, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), Multifactorial Inheritance, Schizophrenia/genetics, LD SCORE REGRESSION, LOCI, Genome-wide association study, Bioinformatics, 0302 clinical medicine, Risk Factors, POLYGENIC RISK, Depression (differential diagnoses), 3. Good health, Phenotype, Schizophrenia, Meta-analysis, MENDELIAN RANDOMIZATION, Genome-Wide Association Study/methods, Major depressive disorder, Female, Depressive Disorder, Major/genetics, EUROPE 2010, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, ddc:570, MENTAL-DISORDERS, Mendelian randomization, SYSTEMATIC ANALYSIS, Genetics, medicine, Journal Article, Humans, Genetic Predisposition to Disease, METAANALYSIS, EDUCATIONAL-ATTAINMENT, Depressive Disorder, Major, Case-control study, Case-Control Studies, medicine.disease, Genetic architecture, BODY-MASS INDEX, 030104 developmental biology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened\ud risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified\ud 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and\ud implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved\ud in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression\ud with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were\ud putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry\ud lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression\ud and imply that a continuous measure of risk underlies the clinical phenotype.
Published: 2018

38. The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy

Author: Ingrid E. Scheffer, Trupti Jadhav, Mel Michel G Villaluz, J. Helen Cross, and Lysa Boissé Lomax
Subjects: Male, Drug Resistant Epilepsy, Pediatrics, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Encephalopathy, Cohort Studies, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Developmental Neuroscience, Dravet syndrome, 030225 pediatrics, medicine, Humans, Retrospective Studies, business.industry, Retrospective cohort study, medicine.disease, Treatment Outcome, Brain Injuries, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Etiology, Female, Neurology (clinical), Diet, Ketogenic, business, 030217 neurology & neurosurgery, Ketogenic diet
Abstract: AIM: Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. METHOD: The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. RESULTS: Seven of the nine patients were responders at 3 months. INTERPRETATION: Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. WHAT THIS PAPER ADDS: The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology.
Published: 2018

39. A recurrent de novo missense mutation in UBTF causes developmental neuroregression

Author: May Christine V. Malicdan, Jun Tian, Lawrence T. Reiter, Chris Balak, Kevin A. Hope, Michel G. Tremblay, David R. Adams, Harper B Fauni, Jianfeng Xiao, Camilo Toro, Alexis L Franks, Roderick T. Hori, Amy Goldstein, William A. Gahl, Mark S. LeDoux, Lynne A. Wolfe, Mohammad Moshahid Khan, Tom Moss, and Cynthia J. Tifft
Subjects: Gait Ataxia, Male, 0301 basic medicine, Mutation, Missense, RNA polymerase II, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), RNA, Ribosomal, 18S, Genetics, medicine, Humans, Missense mutation, Molecular Biology, Exome, Transcription factor, Genetics (clinical), 030304 developmental biology, 0303 health sciences, biology, Dysarthria, Articles, General Medicine, Corrigenda, Magnetic Resonance Imaging, RRNA transcription, Hypotonia, Pedigree, 030104 developmental biology, Child, Preschool, Cancer research, biology.protein, Muscle Hypotonia, Female, medicine.symptom, Pol1 Transcription Initiation Complex Proteins, 030217 neurology & neurosurgery
Abstract: UBTF (upstream binding transcription factor) exists as two isoforms; UBTF1 regulates rRNA transcription by RNA polymerase 1, whereas UBTF2 regulates mRNA transcription by RNA polymerase 2. Herein, we describe 4 patients with very similar patterns of neuroregression due to recurrent de novo mutations in UBTF (GRCh37/hg19, NC_000017.10: g.42290219C > T, NM_014233.3: c.628G > A) resulting in the same amino acid change in both UBTF1 and UBTF2 (p.Glu210Lys [p.E210K]). Disease onset in our cohort was at 2.5 to 3 years and characterized by slow progression of global motor, cognitive and behavioral dysfunction. Notable early features included hypotonia with a floppy gait, high-pitched dysarthria and hyperactivity. Later features included aphasia, dystonia, and spasticity. Speech and ambulatory ability were lost by the early teens. Magnetic resonance imaging showed progressive generalized cerebral atrophy (supratentorial > infratentorial) with involvement of both gray and white matter. Patient fibroblasts showed normal levels of UBTF transcripts, increased expression of pre-rRNA and 18S rRNA, nucleolar abnormalities, markedly increased numbers of DNA breaks, defective cell-cycle progression, and apoptosis. Expression of mutant human UBTF1 in Drosophila neurons was lethal. Although no loss-of-function variants are reported in the Exome Aggregation Consortium (ExAC) database and Ubtf−/− is early embryonic lethal in mice, Ubtf+/− mice displayed only mild motor and behavioral dysfunction in adulthood. Our data underscore the importance of including UBTF E210K in the differential diagnosis of neuroregression and suggest that mainly gain-of-function mechanisms contribute to the pathogenesis of the UBTF E210K neuroregression syndrome.
Published: 2018

40. SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice

Author: Liang Zhao, Ee Ting Ng, Tevin Chui-Ying Chau, Peter Koopman, Sunny Hartwig, Michel G. Arsenault, and Enya Longmuss
Subjects: Male, 0301 basic medicine, Homeobox protein NANOG, endocrine system, medicine.medical_specialty, Somatic cell, SOX9, Biology, SOXC Transcription Factors, SOX Transcription Factors, Mice, 03 medical and health sciences, Fetus, Internal medicine, Testis, Morphogenesis, medicine, Animals, Cell Lineage, Spermatogenesis, Enhancer, Molecular Biology, Gonad morphogenesis, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Biology, Sex-Determining Region Y Protein, Cell biology, Germ Cells, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Female, Germ line development, Germ cell, Developmental Biology
Abstract: The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation. Finally, our data reveal that SOX4 (and, to a lesser extent, SOX11 and -12) repressed transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads, raising the possibility that SOXC proteins may function as transcriptional repressors in a context-dependent manner.
Published: 2017

41. Heritability of Behavioral Problems in 7-Year Olds Based on Shared and Unique Aspects of Parental Views

Author: Laura W. Wesseldijk, Catharina E. M. van Beijsterveldt, Dorret I. Boomsma, Jouke-Jan Hottenga, Meike Bartels, Michel G. Nivard, Christel M. Middeldorp, Iryna O. Fedko, Adult Psychiatry, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, and APH - Methodology
Subjects: 0301 basic medicine, Parents, Male, Netherlands Twin Register (NTR), health care facilities, manpower, and services, Twins, Child Behavior, CBCL, Developmental psychology, Fathers, Fathers/psychology, Models, Surveys and Questionnaires, Genetics(clinical), Child Behavior Checklist, Child, Genetics (clinical), Original Research, Netherlands, 05 social sciences, Mothers/psychology, Psychometrics/methods, Female, Psychology, Twins/genetics, 050104 developmental & child psychology, Psychopathology, Parents/psychology, Genetic correlation, Psychometrics, Child psychopathology, Child Behavior Disorders/genetics, education, Mothers, Problem Behavior/psychology, Context (language use), Child Behavior Disorders, Behavioral problems, behavioral disciplines and activities, Heritability, 03 medical and health sciences, Child Behavior/psychology, Genetic, Genetics, Humans, 0501 psychology and cognitive sciences, CBCL 6–18, Ecology, Evolution, Behavior and Systematics, Problem Behavior, Models, Genetic, Parental ratings, Reproducibility of Results, Twin study, 030104 developmental biology
Abstract: In studies of child psychopathology, phenotypes of interest are often obtained by parental ratings. When behavioral ratings are obtained in the context of a twin study, this allows for the decomposition of the phenotypic variance, into a genetic and a non-genetic part. If a phenotype is assessed by a single rater, heritability is based on the child’s behavior as expressed in the presence of that particular rater, whereas heritability based on assessments by multiple raters allows for the estimation of the heritability of the phenotype based on rater agreement, as well as the heritability of the rater specific view of the behavior. The aim of this twin study was to quantify the rater common and rater specific contributions to the variation in children’s behavioral problems. We estimated the heritability of maternal and paternal ratings of the Child Behavior Checklist (CBCL) 6–18 empirical emotional and behavioral problem scales in a large sample of 12,310 7-year old Dutch twin pairs. Between 30 and 59% of variation in the part of the phenotype parents agree upon was explained by genetic effects. Common environmental effects that make children in the same family similar explained less variance, ranging between 0 and 32%. For unique views of their children’s behavioral problems, heritability ranged between 0 and 20% for maternal and between 0 and 22% for paternal views. Between 7 and 24% of the variance was accounted for by common environmental factors specific to mother and father’s views. The proportion of rater shared and rater specific heritability can be translated into genetic correlations between parental views and inform the design and interpretation of results of molecular genetic studies. Genetic correlations were nearly or above 0.7 for all CBCL based psychopathology scales. Such large genetic correlations suggest two practical guidelines for genome-wide association studies (GWAS): when studies have collected data from either fathers or mothers, the shared genetic aetiology in parental ratings indicates that is possible to analyze paternal and maternal assessments in a single GWAS or meta-analysis. Secondly, if a study has collected information from both parents, a gain in statistical power may be realized in GWAS by the simultaneous analysis of the data. Electronic supplementary material The online version of this article (doi:10.1007/s10519-016-9823-1) contains supplementary material, which is available to authorized users.
Published: 2017

42. Psychopathology in 7-year-old children: Differences in maternal and paternal ratings and the genetic epidemiology

Author: Catharina E. M. van Beijsterveldt, Dorret I. Boomsma, Michel G. Nivard, Meike Bartels, Laura W. Wesseldijk, Christel M. Middeldorp, Iryna O. Fedko, Adult Psychiatry, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, Biological Psychology, APH - Personalized Medicine, and APH - Methodology
Subjects: Male, Parents, Netherlands Twin Register (NTR), Shared environment, Twins, 050109 social psychology, Psychology, Child, Fathers, 0302 clinical medicine, Surveys and Questionnaires, Psychology, parental ratings, Child, Genetics (clinical), Research Articles, Psychology, Child/methods, Netherlands, Molecular Epidemiology, Molecular Epidemiology/methods, Psychopathology, Mental Disorders, rater bias, shared environment, 05 social sciences, Variance (accounting), 3. Good health, Psychopathology/methods, Psychiatry and Mental health, Anxiety, Female, medicine.symptom, Clinical psychology, Research Article, Mothers, Clinical settings, Affect (psychology), 03 medical and health sciences, Cellular and Molecular Neuroscience, Bias, SDG 3 - Good Health and Well-being, medicine, Humans, 0501 psychology and cognitive sciences, Reproducibility of Results, Heritability, Twins/psychology, Child/methods, Genetic epidemiology, 030217 neurology & neurosurgery, Mental Disorders/epidemiology
Abstract: The assessment of children's psychopathology is often based on parental report. Earlier studies have suggested that rater bias can affect the estimates of genetic, shared environmental and unique environmental influences on differences between children. The availability of a large dataset of maternal as well as paternal ratings of psychopathology in 7-year old children enabled (i) the analysis of informant effects on these assessments, and (ii) to obtain more reliable estimates of the genetic and non-genetic effects. DSM-oriented measures of affective, anxiety, somatic, attention-deficit/hyperactivity, oppositional-defiant, conduct, and obsessive-compulsive problems were rated for 12,310 twin pairs from the Netherlands Twin Register by mothers (N = 12,085) and fathers (N = 8,516). The effects of genetic and non-genetic effects were estimated on the common and rater-specific variance. For all scales, mean scores on maternal ratings exceeded paternal ratings. Parents largely agreed on the ranking of their child's problems (r 0.60-0.75). The heritability was estimated over 55% for maternal and paternal ratings for all scales, except for conduct problems (44-46%). Unbiased shared environmental influences, i.e., on the common variance, were significant for affective (13%), oppositional (13%), and conduct problems (37%). In clinical settings, different cutoffs for (sub)clinical scores could be applied to paternal and maternal ratings of their child's psychopathology. Only for conduct problems, shared environmental and genetic influences explain an equal amount in differences between children. For the other scales, genetic factors explain the majority of the variance, especially for the common part that is free of rater bias. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.
Published: 2017

43. Short communication: Genetic association between schizophrenia and cannabis use

Author: Michel G. Nivard, Dorret I. Boomsma, Jacqueline M. Vink, Alberto Sainz Cort, Nathan A. Gillespie, Karin J. H. Verweij, Abdel Abdellaoui, Lannie Ligthart, Gonneke Willemsen, Camelia C. Minică, Jouke-Jan Hottenga, Harmen H.M. Draisma, Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Personalized Medicine, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, APH - Methodology, and Academic Medical Center
Subjects: Netherlands Twin Register (NTR), Adult, Male, Multifactorial Inheritance, medicine.medical_specialty, Adolescent, Marijuana Smoking, Toxicology, Genetic correlation, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Journal Article, Diseases in Twins, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Pharmacology (medical), Registries, Psychiatry, Aged, Netherlands, Genetic association, Aged, 80 and over, Pharmacology, biology, Middle Aged, Cannabis use, medicine.disease, biology.organism_classification, Regression, 030227 psychiatry, Psychiatry and Mental health, Phenotype, Sample size determination, Schizophrenia, Female, Cannabis, Psychology, Developmental Psychopathology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Item does not contain fulltext Background and aim: Previous studies have shown a relationship between schizophrenia and cannabis use. As both traits are substantially heritable, a shared genetic liability could explain the association. We use two recently developed genomics methods to investigate the genetic overlap between schizophrenia and cannabis use. Methods: Firstly, polygenic risk scores for schizophrenia were created based on summary statistics from the largest schizophrenia genome-wide association (GWA) meta-analysis to date. We analysed the association between these schizophrenia polygenic scores and multiple cannabis use phenotypes (lifetime use, regular use, age at initiation, and quantity and frequency of use) in a sample of 6,931 individuals. Secondly, we applied LD-score regression to the GWA summary statistics of schizophrenia and lifetime cannabis use to calculate the genome-wide genetic correlation. Results: Polygenic risk scores for schizophrenia were significantly (alpha
Published: 2017

44. Post-traumatic stress disorder in a sample of Syrian refugees in Lebanon

Author: Michel Soufia, Nada Zahreddine, Mustafa A. Almustafa, Francois Kazour, Michel G. Maragel, Sami Richa, and Ramzi Haddad
Subjects: Adult, Male, medicine.medical_specialty, lcsh:RC435-571, Refugee, Prevalence, Sample (statistics), Logistic regression, behavioral disciplines and activities, Stress Disorders, Post-Traumatic, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, lcsh:Psychiatry, mental disorders, Humans, Medicine, 030212 general & internal medicine, Lebanon, Young adult, Psychiatry, Mini-international neuropsychiatric interview, Refugees, Syria, business.industry, Traumatic stress, Middle Aged, Mental health, Psychiatry and Mental health, Clinical Psychology, Female, business, 030217 neurology & neurosurgery, Demography
Abstract: Introduction Lebanon is the main hosting country for the Syrian crisis, with more than one million Syrian refugees. The objective of this study was to determine the prevalence of post-traumatic stress disorder (PTSD), and identify its possible predictors, in a sample of Syrian refugees living in camps in Lebanon. Method We conducted a household survey on Syrian refugees between 18 and 65years old in 6 camps of the Central Bekaa region, using the Mini International Neuropsychiatric Interview (M.I.N.I.) as a diagnostic tool. Results Among the 452 respondents, we found a lifetime prevalence of PTSD of 35.4%, and a point prevalence of 27.2%. The lifetime prevalence of SUD was 1.99% and the point prevalence 0.66%. Multivariate logistic regression could not identify any predictor of current PTSD among a list of demographic variables, but identified the Syrian hometown as a significant predictor of lifetime PTSD ( p =.013), with refugees from Aleppo having significantly more PTSD than those coming from Homs (adjusted OR 2.14, 95% CI [1.28, 3.56], p =.004). Discussion PTSD was a real mental health issue in our sample of adult Syrian refugees in Central Bekaa camps, unlike SUD.
Published: 2017

45. The 12th Edition of the Scientific Days of the National Institute for Infectious Diseases 'Prof. Dr. Matei Bals' and the 12th National Infectious Diseases Conference

Author: Cristian-Mihail Niculae, Eliza Manea, Raluca Jipa, Simona Merisor, Ruxandra Moroti, Serban Benea, Adriana Hristea, Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Dana Mărculescu, Magdalena Lorena Andrei, Veronica Ilie, Marcela Popa, Coralia Bleotu, Carmen Chifiriuc, Mircea Ioan Popa, Adrian Streinu-Cercel, Alina Orfanu, Cristina Popescu, Anca Leuștean, Remulus Catană, Anca Negru, Alexandra Badea, Radu Orfanu, Cătălin Tilișcan, Victoria Aramă, Ştefan Sorin Aramă, Constanța-Angelica Vișan, Anca-Cristina Drăgănescu, Anuța Bilașco, Camelia Kouris, Mădălina Merișescu, Magdalena Vasile, Diana-Maria Slavu, Sabina Vintilă, Endis Osman, Alina Oprea, Sabina Sandu, Monica Luminos, Anca Leuştean, Gabriel Adrian Popescu, Ramona Georgiana Stanculete, Ana Vaduva Enoiu, Adelina Raluca Marinescu, Voichita Lazureanu, Adelina-Raluca Marinescu, Alexandru Crișan, Voichița Lăzureanu, Virgil Musta, Narcisa Nicolescu, Ruxandra Laza, Anca-Ruxandra Negru, Daniela-Ioana Munteanu, Raluca Mihăilescu, Olga Dorobăț, Alexandru Rafila, Emilia Căpraru, Marius Niculescu, Rodica Marinescu, Olivera Lupescu, Vlad Predescu, Daniela Tălăpan, Ramona Ștefania Popescu, Luminița Bradu, Dragoș Florea, Daniela Anicuta Leca, Elena Bunea, Andra Teodor, Egidia Miftode, Gheorghiță Jugulete, Anamaria Dobrotă, Adina Ilie, Liliana Lucia Preoțescu, Nicoleta Irimescu, Irina Panait, Cristian Niculae, Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Șerban Benea, Mona Popoiu, Livia Dragonu, Augustin Cupşa, Iulian Diaconescu, Irina Niculescu, Lucian Giubelan, Florentina Dumitrescu, Andreea Cristina Stoian, Camelia Guţă, Simona Puiu, Bunescu Irina, Marilyse Vallée, Ann Huletsky, Dominique K. Boudreau, Ève Bérubé, Richard Giroux, Jean Longtin, Yves Longtin, Michel G. Bergeron, Cleo Nicoleta Roșculeț, Dalila-Ana Toma, Catrinel Ciuca, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Tudor Vladoiu, Doina Iovănescu, Michaela Oana, Simona Costin, Maria Magdalena Moțoi, Olga Mihaela Dorobăț, Alexandru Mihai, Cleo Roşculeț, Gabriel-Adrian Popescu, Adrian Abagiu, Ruxandra Moroti-Constantinescu, Otilia Benea, Mădălina Simoiu, Rodica Bacruban, Ioana Bădicuț, Alina Borcan, Mihnea Hurmuzache, Georgiana Enache, Alexandra Ciocan, Mircea Bararu, Madalina Popazu, Doina Viorica Iovănescu, Cătălin Gabriel Apostolescu, Dalila Toma, Laura Iliescu, Georgiana Minzala, Letitia Toma, Mihaela Baciu, Alina Tanase, Carmen Orban, Victor Pantea, Gheorghe Placinta, Valentin Cebotarescu, Lilia Cojuhari, Paulina Jimbei, Cristina Dragomirescu, Cristina Murariu, Laurențiu Stratan, Daniela Munteanu, Raluca Năstase, Violeta Molagic, Mihaela Rădulescu, Ioan Diaconu, Iulia Bodosca, Violeta Niță, Raluca Mihaela Năstase, Iulia Bodoșca, Ioan Alexandru Diaconu, Yagmur Erturk, Claudiu Mihai Șchiopu, Angelica Tenita, Ștefan Sorin Aramă, Simona Alexandra Iacob, Diana Gabriela Iacob, Mioara Predescu, Alexandra Mărdărescu, Mihai Săndulescu, Catrinel Olimpia Ciuca, Dalila Ana Toma, Cristina Elena Mitu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Monica Andreea Stoica, Daniela Manolache, Gabriela Jana Ceapraga, Gabriela Mircea, Ionel Durbală, Irina Russu, Tiberiu Holban, Tatiana Pantilimonov, Galina Chiriacov, Arcadie Macvovei, Elena Scorohodico, Oleg Dmitriev, Diana Alexandra Costache, Anca Benea, Elisabeta Benea, Mihai Mitran, Carmen Georgescu, Loredana Mitran, Simona Vladareanu, Andreea Ioana Magirescu, Viorica Andreev, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc, Ina Isac, Iulia Gabriela Șerban, Ghiulendan Resul, Consuela Marcaș, Iosif Marincu, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Anca Tudor, Daliborca Vlad, Livius Tirnea, Nurcan Baydaroglu, Gabriela Ceapraga, Mariana Pagute, Carmen Dorobăț, Ioan-Alexandru Diaconu, Daniela Ion, Luciana Nichita, Alexandra Diaconu, Irina Duport-Dodot, Mariana Mărdărescu, Cristina Petre, Marieta Iancu, Rodica Ungurianu, Alina Cibea, Ruxandra Drăghicenoiu, Ana Maria Tudor, Delia Vlad, Sorin Petrea, Carina Matei, Dan Oțelea, Carmen Crăciun, Cristian Anghelina, Elena Dumea, Sorin Rugină, Lucian Cristian Petcu, Stela Halichidis, Simona Claudia Cambrea, Carmen Chiriac, Nina-Ioana Bodnar, Iringo-Erzsebet Zaharia-Kezdi, Cristina Gîrbovan, Andrea Incze, Anca Meda Georgescu, Eugenia Panaitescu, Manole Cojocaru, Vochita Laurențiu, Vochita Andreia, Opreanu Radu, Trinca Bogdan, Rosca Ovidiu, Marincu Iosif, Ramona Zamfir, Alina Angelescu, Alena Andreea Popa, Liana Gavriliu, Alena-Andreea Popa, Georgeta Ducu, Daniela Camburu, Alina Cozma, Manuela Podani, Roxana Dumitriu, Augustin Cupșa, Loredana Ionescu, Adrian Octavian Abagiu, Loredana Nicoleta Stoica, Catrinel Blaga, Archontis Koulosousas, Roxana Ștefănescu, Alice Atomoaie, Florentina Paraschiv, Florin Matache Duna, Rodica Olteanu, Roxana Ion, Alexandra Zota, Isra Ennour Jaballah, Lara Mahfoud, Georgeta Preda, Magda Constantin, Ilinca Nicolae, Corina Daniela Ene, Mădălina Irina Mitran, Vasile Benea, Mircea Tampa, Simona Roxana Georgescu, Iulia Cristina Bodoșca, Sorin Aramă, Iuliana Caramăngiu, Ovidiu Rosca, Monica Cialma, Radu Opreanu, Laurențiu Vochita, Vlad Murărescu, Marilena Palaghiță, Cornel Camburu, Irina Duşan, Andreea Bîrlad, Victor Daniel Miron, Anca Cristina Drăgănescu, Daniela Pițigoi, Monica Luminița Luminos, Sabina Șchiopu, Magda Vasile, Mihaela Ionică, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Lucia Tudor, Cristina Negulescu, Olga Adriana Caliman-Sturdza, Cleo Roșculeț, Bogdana Manu, Ana Vaduva-Enoiu, Voichita Elena Lazureanu, Elena-Violeta Niță, Sînziana Dumitru, Anca Ruxandra Negru, Ligia Ionescu, Liliana Ion, Marioara Neacșu, Cristina Iulia Mitran, George Ciprian Pribac, Mirandolina Prisca, Fulvia Ursoiu, Carmen Neamtu, Bogdan Totolici, Coralia Cotoraci, Aurel Ardelean, Simona Elena Albu, Mara Carsote, Beatrice Miclăuș, Diana Mihai, Cristina Vasiliu, Corina Gorgoi, Amelia Blescun, Gelu Breaza, Sabina Vintila, Felicia Mihai, Meilin Omer, Cornel Dragan, Daniela Pitigoi, Mirela Ciucu, Marius-Dan Ionescu, Cristina Roskanovic, Valentina Barbu, Ramona-Alexandra Zamfir, Alexandra-Sînziana Dumitru, Viorica Ispas, Diana Oana Leahu, Cristina Maria Safta, Mihaela Anca Benea, Octavian Munteanu, Roxana Bohâlțea, Livia Trașcă, Monica Cîrstoiu, Mădălina Georgescu, Alina Elena Ivanciuc, Mihaela Lazar, Teodora Ionescu, Carmen Maria Cherciu, Cristina Țecu, Maria Elena Mihai, Maria Nițescu, Delia Azamfire, Aura Dumitrescu, Elena Ianosik, Daniela Leca, Elena Duca, Codrina Bejan, Emanoil Ceaușu, Simin-Aysel Florescu, Corneliu Popescu, Grațiela Târdei, Codrina Juganariu, Emilia Lupulescu, Ligia Rodina, Maria Elena Cocuz, Andreea Stoian, Mihaela Ionica, Otilia-Elisabeta Benea, Maria-Cristina Sîrbu, AnaMaria Dobrotă, Roxana Duda, Cristiana Cerasella Dragomirescu, Sergiu Fendrihan, Ecaterina Scortan, Corneliu P. Popescu, Șerban N. Benea, Andra E. Petcu, Iuliana A. Podea, Raluca E. Jipa, Raluca M. Hrișcă, Manuela Nica, Simona Merișor, Cristian M. Nicolae, Simin A. Florescu, Irina M. Dumitru, Ruxandra V. Moroti, Bogdan Nițescu, Iulia Monica Mustaţă, Sorina Claudia Boldeanu, Florentina Furtunescu, Mihaela Gheorghe, Adriana Slavcovici, Raluca Tripon, Roxana Iubu, Cristian Marcu, Mihaela Sabou, Monica Muntean, Ion Chiriac, Liviu Tazlavanu, Roxana Cernat, Kezdi Iringo, Andrei Vâță, Manuela Arbune, Teodora Moisil, Corina-Daniela Ene, Roxana Simona Georgescu, Cosmin-Victor Ene, Marilena Ciortea, Lucreția Dulgheru, Mihaela Cătălina Luca, Ioana-Alina Harja-Alexa, Roxana Nemescu, Mădălina Popazu, Andrei Ștefan Luca, Gabriela Bancescu, Bogdan Dabu, Adrian Bancescu, Adina Elena Ilie, Săftica-Mariana Pohrib, Maria-Sabina Tache, Ion Aurel Iliescu, Cristina Tecu, Maria-Elena Mihai, Mihaela Lazăr, Carmen Cherciu, Alina Ivanciuc, Mirela Paliu, Manuela Curescu, Bianca Cerbu, Irina Bunescu, Ana Pasnin, Stela Semeniuc, and Raisa Popovici
Subjects: Lung Diseases, Male, 0301 basic medicine, medicine.medical_specialty, Daclatasvir, Sofosbuvir, Mycobacterium avium complex, 030106 microbiology, Pharmacy, Microbial Sensitivity Tests, Clostridium Difficile Infection, Azithromycin, Meeting Abstracts, lcsh:Infectious and parasitic diseases, Cerebral Spinal Fluid, 03 medical and health sciences, Chronic hepatitis, Risk Factors, Clarithromycin, Drug Resistance, Bacterial, medicine, Humans, lcsh:RC109-216, Serum Albumin, Aged, Mycobacterium avium-intracellulare Infection, Retrospective Studies, business.industry, Sputum, Fecal Microbiota Transplantation, Middle Aged, Anti-Bacterial Agents, C-Reactive Protein, Treatment Outcome, Infectious Diseases, Parasitology, Progressive Multifocal Leukoencephalopathy, Drug resistance, Family medicine, Multivariate Analysis, Tropical medicine, Female, Respiratory Syncytial Virus, Macrolides, Drug therapy, Tomography, X-Ray Computed, business, Research Article, medicine.drug
Abstract: Table of contents A1 The outcome of patients with recurrent versus non-recurrent pneumococcal meningitis in a tertiary health-care hospital in Bucharest Cristian-Mihail Niculae, Eliza Manea, Raluca Jipa, Simona Merisor, Ruxandra Moroti, Serban Benea, Adriana Hristea A2 Influence of bacteriophages on sessile Gram-positive and Gram-negative bacteria Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Dana Mărculescu, Magdalena Lorena Andrei, Veronica Ilie, Marcela Popa, Coralia Bleotu, Carmen Chifiriuc, Mircea Ioan Popa, Adrian Streinu-Cercel A3 The utility of inflammatory biomarkers in the prognostic evaluation of septic patients – past, present and future Alina Orfanu, Cristina Popescu, Anca Leuștean, Remulus Catană, Anca Negru, Alexandra Badea, Radu Orfanu, Cătălin Tilișcan, Victoria Aramă, Ştefan Sorin Aramă A4 Etiologic and clinical features of bacterial meningitis in infants Constanța-Angelica Vișan, Anca-Cristina Drăgănescu, Anuța Bilașco, Camelia Kouris, Mădălina Merișescu, Magdalena Vasile, Diana-Maria Slavu, Sabina Vintilă, Endis Osman, Alina Oprea, Sabina Sandu, Monica Luminos A5 The diagnostic and prognostic role of neutrophil to lymphocyte count ratio in sepsis Alina Orfanu, Victoria Aramă, Ştefan Sorin Aramă, Anca Leuştean, Remulus Catană, Anca Negru, Gabriel Adrian Popescu, Cristina Popescu A6 Whooping cough in a HIV positive patient Ramona Georgiana Stanculete, Ana Vaduva Enoiu, Adelina Raluca Marinescu, Voichita Lazureanu A7 Cronobacter sakazakii sepsis in varicella patient Adelina-Raluca Marinescu, Alexandru Crișan, Voichița Lăzureanu, Virgil Musta, Narcisa Nicolescu, Ruxandra Laza A8 Anaerobes an underdiagnosed cause of prosthesis joint infection Anca-Ruxandra Negru, Daniela-Ioana Munteanu, Raluca Mihăilescu, Remulus Catană, Olga Dorobăț, Alexandru Rafila, Emilia Căpraru, Marius Niculescu, Rodica Marinescu, Olivera Lupescu, Vlad Predescu, Adrian Streinu-Cercel, Victoria Aramă, Daniela Tălăpan A9 Streptococcus pneumoniae meningitis presenting with normal CSF – case presentation Ramona Ștefania Popescu, Luminița Bradu, Dragoș Florea, Adrian Streinu-Cercel A10 Extrapulmonary manifestations of infection with Mycoplasma pneumoniae – study on 24 cases Daniela Anicuta Leca, Elena Bunea, Andra Teodor, Egidia Miftode A11 The molecular diagnosis of severe bacterial sepsis in pediatric population Mădălina Merișescu, Gheorghiță Jugulete, Adrian Streinu-Cercel, Dragoș Florea, Monica Luminos A12 Acute Staphylococcus aureus endocarditis with multiple septic complications in a patient with diabetes mellitus – case presentation Ramona Ștefania Popescu, Anamaria Dobrotă, Adina Ilie, Liliana Lucia Preoțescu A13 Is Streptococcus suis meningitis an under-diagnosed zoonosis? Adriana Hristea, Raluca Jipa, Nicoleta Irimescu, Irina Panait, Eliza Manea, Simona Merisor, Cristian Niculae, Daniela Tălăpan A14 Klebsiella pneumoniae isolated from blood. Antimicrobial resistance – past and present Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Șerban Benea, Alexandru Rafila, Olga Dorobăț, Mona Popoiu A15 Antibiotics resistance in Staphylococcus aureus isolated from blood cultures Livia Dragonu, Augustin Cupşa, Iulian Diaconescu, Irina Niculescu, Lucian Giubelan, Florentina Dumitrescu, Andreea Cristina Stoian, Camelia Guţă, Simona Puiu A16 Predominance of CTX-M enzymes in extended-spectrum β-lactamase-producing Enterobacteriaceae in two hospitals of Quebec City Bunescu Irina, Marilyse Vallée, Ann Huletsky, Dominique K. Boudreau, Ève Bérubé, Richard Giroux, Jean Longtin, Yves Longtin, Michel G. Bergeron A17 Postoperative meningoencephalitis with Acinetobacter baumannii XDR – a therapeutic challenge - Case report Cleo Nicoleta Roșculeț, Dalila-Ana Toma, Catrinel Ciuca, Daniela Tălăpan, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Tudor Vladoiu, Doina Iovănescu A18 Septic arthritis with Burkholderia cepacia Michaela Oana, Simona Costin A19 A novel approach for managing hard-to-treat infections Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Maria Magdalena Moțoi, Mircea Ioan Popa, Adrian Streinu-Cercel A20 Nineteen months surveillance for multidrug resistant organisms (MDRO) by detecting asymptomatic colonization Daniela Tălăpan, Olga Mihaela Dorobăț, Mona Popoiu, Alexandru Mihai, Doina Iovănescu, Cleo Roşculeț, Cătălin Apostolescu, Gabriel-Adrian Popescu, Adrian Abagiu, Ruxandra Moroti-Constantinescu, Adriana Hristea, Victoria Aramă, Otilia Benea, Mădălina Simoiu, Rodica Bacruban, Adrian Streinu-Cercel, Alexandru Rafila A21 Antimicrobial resistance of Gram-positive cocci isolated from clinical specimens in the National Institute of Infectious Diseases “Prof Dr. Matei Balș” between 2009–2015 Olga Mihaela Dorobăț, Daniela Tălăpan, Alexandru Mihai, Ioana Bădicuț, Mona Popoiu, Alina Borcan, Alexandru Rafila A22 The high percentage of carbapenem-resistant Gram-negative bacilli in Romania: an analysis and some proposals Gabriel Adrian Popescu A23 Etiological, clinical and therapeutic considerations on 78 cases of healthcare associated meningitis or ventriculitis admitted in the “Sf. Parascheva” infectious diseases clinical hospital, Iași, from 2011 to 2015 Mihnea Hurmuzache, Georgiana Enache, Alexandra Ciocan, Mircea Bararu, Madalina Popazu A24 Nosocomial infection dynamics in an Intensive Care Department – an overview (epidemiological and clinical monitoring, advanced therapeutic intervention). Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz Cătălin Gabriel Apostolescu, Viorica Mitescu, Tudor Vladoiu, Dalila Toma, Catrinel Ciuca A25 Safety and efficacy of interferon free treatment in patients with HCV chronic hepatitis- experience of a single Internal Medicine center Laura Iliescu, Georgiana Minzala, Letitia Toma, Mihaela Baciu, Alina Tanase, Carmen Orban A26 Viusid in treatment of chronic viral hepatitis B and C Victor Pantea, Gheorghe Placinta, Valentin Cebotarescu, Lilia Cojuhari, Paulina Jimbei A27 The management of hyperbilirubinemia in HCV cirrhotic patients who underwent therapy with direct acting antivirals Cristina Popescu, Anca Leuștean, Cristina Dragomirescu, Alina Orfanu, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Raluca Năstase, Violeta Molagic, Mihaela Rădulescu, Remulus Catana, Victoria Aramă A28 The efficacy of ombitasvir-paritaprevir/ritonavir, dasabuvir and ribavirin in patients with genotype 1 HCV compensated cirrhosis Cristina Popescu, Laurențiu Stratan, Remulus Catana, Anca Leuștean, Cristina Dragomirescu, Alexandra Badea, Cristina Murariu, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Alina Orfanu, Ioan Diaconu, Anca Negru, Iulia Bodosca, Violeta Niță, Victoria Aramă A29 The efficacy of direct acting antivirals regimen without ribavirin in HCV genotype 1b infected patients with compensated cirrhosis Anca Leuștean, Victoria Aramă, Alina Orfanu, Remulus Catana, Laurențiu Stratan, Cristina Dragomirescu, Cristina Murariu, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Violeta Molagic, Raluca Năstase, Mihaela Rădulescu, Cristina Popescu A30 Liver decompensation during ombitasvir-paritaprevir/ritonavir-dasabuvir and ribavirin regimen in HCV infected patients with Child-Pugh A cirrhosis Cristina Popescu, Cristina Dragomirescu, Anca Leuștean, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Remulus Catană, Alina Orfanu, Raluca Mihaela Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Victoria Aramă A31 The safety of direct acting antivirals in HCV compensated cirrhotic patients - an interim analysis Victoria Aramă, Remulus Catană, Cristina Dragomirescu, Cristina Murariu, Anca Leuștean, Laurențiu Stratan, Alexandra Badea, Alina Orfanu, Anca Negru, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Cristina Popescu A32 The access of patients with HCV compensated cirrhosis to the National Program of therapy with direct acting antivirals Cristina Popescu, Alexandra Badea, Anca Leuștean, Alina Orfanu, Anca Negru, Laurențiu Stratan, Cristina Dragomirescu, Remulus Catană, Cristina Murariu, Violeta Molagic, Raluca Năstase, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Victoria Aramă A33 Severe reactivation of chronic hepatitis B after discontinuation of nucleos(t)ide analogues – a case series Cristina Popescu, Alina Orfanu, Anca Leuștean, Alexandra Badea, Laurențiu Stratan, Remulus Catană, Cătălin Tilișcan, Victoria Aramă A34 The dynamic of hematological disorders during direct acting antivirals therapy for HCV compensated cirrhosis Cristina Popescu, Cristina Murariu, Cristina Dragomirescu, Anca Leuștean, Laurențiu Stratan, Alina Orfanu, Alexandra Badea, Remulus Catană, Anca Negru, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Mihaela Năstase, Ioan Alexandru Diaconu, Iulia Bodoșca, Violeta Niță, Victoria Aramă A35 Behaviors, attitudes and risk factors for viral hepatitis in international medical students vs. the general population in Romania Yagmur Erturk, Oana Săndulescu, Alina Cristina Neguț, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel, Anca Streinu-Cercel A36 Characteristics of hepatitis C virus reactivation due to immunosuppressive therapy in Romanian HCV infected patients with hematological malignancies Violeta Molagic, Cătălin Tilișcan, Cristina Popescu, Raluca Mihăilescu, Daniela Munteanu, Raluca Năstase, Anca Negru, Angelica Tenita, Victoria Aramă, Ștefan Sorin Aramă A37 The dynamic IFN-gamma serum levels during successful peginterferon-a 2a/ribavirin therapy in HCV chronic infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A38 Overlapping risk factors for transmission of HBV, HCV and HIV in the general population in Romania Anca Streinu-Cercel, Oana Săndulescu, Mioara Predescu, Alexandra Mărdărescu, Cătălin Tilișcan, Mihai Săndulescu, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel A39 Acute hepatitis - an uncommon neurological complication Cleo Nicoleta Roșculeț, Catrinel Olimpia Ciuca, Dalila Ana Toma, Cătălin Gabriel Apostolescu, Andrei Rogoz, Cristina Elena Mitu, Andrei Stangaciu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Doina Viorica Iovănescu A40 Regression of liver fibrosis following sustained virological response in patients with chronic HCV infection and cirrhosis Oana Săndulescu, Anca Streinu-Cercel, Monica Andreea Stoica, Liliana Lucia Preoțescu, Daniela Manolache, Gabriela Jana Ceapraga, Maria Magdalena Moțoi, Luminița Bradu, Adina Ilie, Gabriela Mircea, Ionel Durbală, Adrian Streinu-Cercel A41 Preliminary results of treatment with sofosbuvir and daclatasvir of patients with chronic hepatitis C Irina Russu, Tiberiu Holban, Tatiana Pantilimonov, Galina Chiriacov, Arcadie Macvovei, Elena Scorohodico, Oleg Dmitriev A42 HIV-syphilis coinfection Diana Alexandra Costache, Anca Benea, Eliza Manea, Cristian Niculae, Raluca Jipa, Adriana Hristea, Elisabeta Benea, Ruxandra Moroti, Șerban Benea A43 Thrombophilia – additional risk factor for the evolution of pregnancy in HIV-positive patients Mihai Mitran, Carmen Georgescu, Loredana Mitran, Simona Vladareanu A44 The incidence of oropharyngeal candidiasis in hospitalized HIV infected pediatric Romanian cohort between 1 January - 31 December 2015 Andreea Ioana Magirescu, Viorica Andreev, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc A45 TB incidence in HIV infected patients during the year of 2015 Viorica Andreev, Andreea Ioana Magirescu, Ina Isac, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc A46 Retrospective analysis of HIV/AIDS deaths recorded in the Clinical Infectious Diseases Hospital, Constanța in the period 01 January 2014–30 June 2016. Epidemiological considerations. Iulia Gabriela Șerban, Ghiulendan Resul, Consuela Marcaș A47 Acute liver failure with favorable evolution in an HIV-HBV coinfected patient Iosif Marincu, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Anca Tudor, Daliborca Vlad, Livius Tirnea A48 Lifestyle impact on HIV management Nurcan Baydaroglu, Alina Cristina Neguț, Oana Săndulescu, Daniela Manolache, Gabriela Ceapraga, Monica Andreea Stoica, Anca Streinu-Cercel, Adrian Streinu-Cercel 49. HIV positive mothers newborns - clinical experience from January 2012 to June 2016 Carmen Manciuc, Mariana Pagute, Cristina Nicolau, Carmen Dorobăț, Alexandra Largu A50 Rediscovering HIV-associated progressive multifocal leukoencephalopathy and HIV encephalopathy: clinical suspicion and subsequent brain autopsies Ioan-Alexandru Diaconu, Laurențiu Stratan, Daniela Ion, Luciana Nichita, Cristina Popescu, Raluca Năstase, Daniela Munteanu, Violeta Molagic, Cătălin Tilișcan, Mihaela Rădulescu, Alexandra Diaconu, Anca Negru, Alina Orfanu, Cristina Dragomirescu, Remulus Catană, Anca Leuștean, Irina Duport-Dodot, Cristina Murariu, Iulia Bodoșca, Violeta Niță, Alexandra Badea, Victoria Aramă A51 Antenatal surveillance of pregnant women with risk behavior and its impact on mother-to-child HIV transmission in Romania Mariana Mărdărescu, Cristina Petre, Marieta Iancu, Rodica Ungurianu, Alina Cibea, Ruxandra Drăghicenoiu, Ana Maria Tudor, Delia Vlad, Sorin Petrea, Carina Matei, Dan Oțelea, Carmen Crăciun, Cristian Anghelina, Alexandra Mărdărescu A52 Noninvasive assessments (APRI, Fib-4, transient elastography) of fibrosis in patients with HIV and HIV/HBV infection Elena Dumea, Adrian Streinu-Cercel, Sorin Rugină, Lucian Cristian Petcu, Stela Halichidis, Simona Claudia Cambrea A53 Undetectable HIV viral load – the main goal in the management of HIV-infected patients Carmen Chiriac, Nina-Ioana Bodnar, Iringo-Erzsebet Zaharia-Kezdi, Cristina Gîrbovan, Andrea Incze, Anca Meda Georgescu A54 LPS serum levels and correlation with immunological, virological and clinical outcome in HIV infected patients Simona Alexandra Iacob, Diana Gabriela Iacob, Eugenia Panaitescu, Monica Luminos, Manole Cojocaru A55 LL37 human cathelicidin serum levels are positively correlated with IFN gamma and alanine aminotransferase level in HCV infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A56 Early diagnosis of pulmonary tuberculosis in a non-compliant HIV/AIDS late presenter patient Vochita Laurențiu, Vochita Andreia, Opreanu Radu, Trinca Bogdan, Rosca Ovidiu, Marincu Iosif A57 Evolution of antiretroviral regimens in naϊve patients in 2016 Ramona Zamfir, Alina Angelescu, Alena Andreea Popa, Raluca Jipa, Ruxandra Moroti, Adriana Hristea, Liana Gavriliu, Șerban Benea, Elisabeta Benea A58 The unfavorable risk factors for HIV infected persons with positive blood cultures hospitalized at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Alena-Andreea Popa, Georgeta Ducu, Daniela Camburu, Alina Cozma, Manuela Podani, Roxana Dumitriu, Liana Gavriliu, Șerban Benea, Elisabeta Benea A59 Epidemiological aspects of HIV infection in Oltenia region Andreea Cristina Stoian, Florentina Dumitrescu, Augustin Cupșa, Lucian Giubelan, Irina Niculescu, Loredana Ionescu, Livia Dragonu A60 HIV risk behaviors and prevalence among patients in methadone maintenance therapy (MMT) from Arena center, Bucharest Adrian Octavian Abagiu, Loredana Nicoleta Stoica, Catrinel Blaga, Archontis Koulosousas, Roxana Ștefănescu, Alice Atomoaie, Florentina Paraschiv, Florin Matache Duna A61 Therapeutic options in a case of severe psoriasis associated with both HIV infection and hepatitis C virus previously treated with fumaric acid esters Rodica Olteanu, Roxana Ion, Alexandra Zota, Isra Ennour Jaballah, Lara Mahfoud, Georgeta Preda, Magda Constantin A62 Prevalence of autoantibodies against gangliosides in asymptomatic HIV-infected patients Ilinca Nicolae, Corina Daniela Ene, Mădălina Irina Mitran, Vasile Benea, Mircea Tampa, Simona Roxana Georgescu A63 Subclinical inflammation in HIV-infected patients undergoing antiretroviral therapy – a cross sectional study Iulia Cristina Bodoșca, Cristina Murariu, Cătălin Tilișcan, Victoria Aramă, Cristina Popescu, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Năstase, Alina Orfanu, Anca Leuștean, Remulus Catană, Anca Negru, Adrian Streinu-Cercel, Sorin Aramă A64 Severe Guillain-Barré syndrome occurring after chickenpox with favorable evolution Iuliana CAramăngiu, Ovidiu Rosca, Monica Cialma, Radu Opreanu, Laurențiu Vochita, Iosif Marincu A65 Echovirus 30 infection with pulmonary and cardiac complications – case report Vlad Murărescu, Marilena Palaghiță, Alina Cristina Neguț, Cornel Camburu, Adrian Streinu-Cercel A66 Herpetic encephalitis with favorable evolution in an adult immunocompetent patient Irina Duşan, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Livius Tirnea, Iosif Marincu A67 Clinical-evolutional aspects in present-day measles Narcisa Nicolescu, Alexandru Crișan, Voichița Lăzureanu, Ruxandra Laza, Virgil Musta, Adelina-Raluca Marinescu, Andreea Bîrlad A68 Pneumococcal superinfection in children with influenza Victor Daniel Miron, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Daniela Pițigoi, Oana Săndulescu, Monica Luminița Luminos A69 Varicella complicated with transverse myelitis - case presentation Monica Luminos, Endis Osman, Magdalena Vasile, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Sabina Șchiopu, Mădălina Merișescu A70 Clinical forms of enterovirus infections during the summer season of 2016 Monica Luminos, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Endis Osman, Sabina Vintilă, Magda Vasile, Mădălina Merișescu A71 Face off – HIV and lymphoma – case series presentation Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Alina Angelescu, Ramona Zamfir, Daniela Camburu, Georgeta Ducu, Alina Cozma, Roxana Dumitriu, Manuela Podani, Șerban Benea, Mihaela Ionică A72 Coxsackie infection complicated by pancytopenia – pediatric case report Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Lucia Tudor, Sabina Vintilă A73 Viral respiratory infections in children in the season 2015–2016 Constanța-Angelica Vișan, Anca Cristina Drăgănescu, Anuța Bilașco, Magda Vasile, Mădălina Merișescu, Camelia Kouris, Cristina Negulescu, Endis Osman, Diana-Maria Slavu, Sabina Vintilă, Daniela Pițigoi, Monica Luminos A75 The severity of A H1N1 Influenza infection in the 2015–2016 season Cleo Roșculeț, Catrinel Olimpia Ciuca, Dalila Toma, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Doina Iovănescu, Cornel Camburu, Bogdana Manu A76 Acute respiratory distress syndrome in a child with measles Ana Vaduva-Enoiu, Ramona Georgiana Stanculete, Adelina Raluca Marinescu, Voichita Elena Lazureanu A77 Management challenges of right-sided infectious endocarditis in an HIV positive patient – case presentation Elena-Violeta Niță, Sînziana Dumitru, Daniela-Ioana Munteanu, Anca Ruxandra Negru, Remulus Catană, Ioan Diaconu, Bogdana Manu, Ligia Ionescu, Liliana Ion, Cătălin Tilișcan, Victoria Aramă A78 Bacterial infection in critical patients with severe A H1N1 influenza virus infection (epidemiology, development, therapeutic decisions) Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Apostolescu, Viorica Mitescu, Tudor Vladoiu, Dalila Toma, Catrinel Ciuca A79 Epidemiological aspects of severe acute respiratory infection cases (SARI) in the season 2015–2016, in the Clinical Hospital of Infectious Diseases – Constanța, Romania Iulia Gabriela Șerban, Marioara Neacșu A80Overexpression of IL-6 trans signaling pathway in viral infections Simona Roxana Georgescu, Vasile Benea, Corina Daniela Ene, Mircea Tampa, Cristina Iulia Mitran, Ilinca Nicolae A81 Acute viral hepatitis B with persistent HBsAg – description and evolution George Ciprian Pribac, Mirandolina Prisca, Fulvia Ursoiu, Carmen Neamtu, Bogdan Totolici, Coralia Cotoraci, Aurel Ardelean A82 Prevalence of cervical pathogens in a population of pregnant female patients monitored in a tertiary care hospital in Bucharest, Romania Simona Elena Albu, Mara Carsote, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Cristina Vasiliu A83 Prevalence of group B Streptococcus during pregnancy in a cohort of patients monitored in a tertiary care hospital in Bucharest, Romania Cristina Vasiliu, Mara Carsote, Corina Gorgoi, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Simona Elena Albu A84 Infectious hematoma in the gastrocnemius muscle – case presentation Amelia Blescun, Gelu Breaza A85 Reflections towards the underexplored HTLV Romanian viral circulation - adult T‐cell leukemia/lymphomas, a case series Sabina Vintila, Felicia Mihai, Meilin Omer, Cornel Dragan, Daniela Pitigoi A86 A febrile confusion syndrome with acute onset – case presentation Mirela Ciucu, Marius-Dan Ionescu, Cristina Roskanovic, Valentina Barbu, Iulian Diaconescu, Florentina Dumitrescu, Irina Niculescu A87 Retrobulbar optic neuritis in a HIV-positive patient - case report Mihaela Ionică, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea A88 A rare presentation of Q fever – case presentation Alexandra-Sînziana Dumitru, Daniela-Ioana Munteanu, Violeta Niță, Cristina Popescu, Iulia Bodosca, Angelica Tenita, Viorica Ispas, Victoria Aramă A89 Tinea incognita – case presentation Vasile Benea, Simona Roxana Georgescu, Mircea Tampa, Diana Oana Leahu, Cristina Maria Safta, Mihaela Anca Benea A90 Incidence and risk factors associated with TORCH infections during pregnancy Oana Săndulescu, Octavian Munteanu, Roxana Bohâlțea, Livia Trașcă, Monica Cîrstoiu A91 Acute respiratory failure in critical patients with sepsis Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Gabriel Apostolescu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Dalila Toma, Catrinel Ciuca A92 Cochleo-vestibular deficit secondary to Granulicatella elegans meningitis Mădălina Georgescu A93 Influenza 2015/2016 – clinical, epidemiological and virological characteristics of cases admitted in three infectious diseases hospitals Daniela Pițigoi, Alina Elena Ivanciuc, Mihaela Lazar, Teodora Ionescu, Carmen Maria Cherciu, Cristina Țecu, Maria Elena Mihai, Maria Nițescu, Rodica Bacruban, Delia Azamfire, Aura Dumitrescu, Elena Ianosik, Daniela Leca, Elena Duca, Andra Teodor, Codrina Bejan, Emanoil Ceaușu, Simin-Aysel Florescu, Corneliu Popescu, Grațiela Târdei, Codrina Juganariu, Emilia Lupulescu A94 Severe complications of varicella requiring hospitalization in previously healthy children in Brașov county Ligia Rodina, Maria Elena Cocuz A95 Clinical forms of Clostridium difficile colitis in children Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Endis Osman A96 Community-acquired pneumonia – demographic, clinical and etiological aspects Irina Niculescu, Augustin Cupșa, Iulian Diaconescu, Florentina Dumitrescu, Livia Dragonu, Andreea Stoian, Lucian Giubelan, Cristina Roskanovic A97 Acute myocarditis in an adult patient with chickenpox - Case report Ramona-Alexandra Zamfir, Mihaela Ionica, Otilia-Elisabeta Benea A98 Caustic oropharyngeal wound with acute group F streptococcal superinfection mimicking diphtheria – case report and differential diagnosis Maria-Cristina Sîrbu, AnaMaria Dobrotă, Alina Cristina Neguț, Roxana Duda, Rodica Bacruban, Daniela Pițigoi, Cristiana Cerasella Dragomirescu, Daniela Tălăpan, Olga Dorobăț, Adrian Streinu-Cercel, Anca Streinu-Cercel A99 Clostridium difficile infection in HIV-positive patients admitted in the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Mihaela Ionica, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea A100 Title: Epidemiology of Candida oral infections (stomatitis) in Romania Sergiu Fendrihan, Ecaterina Scortan, Mircea Ioan Popa A101 Anthrax case series in south-eastern Romania Corneliu P Popescu, Șerban N Benea, Andra E Petcu, Adriana Hristea, Adrian Abagiu, Iuliana A Podea, Raluca E Jipa, Georgeta Ducu, Raluca M Hrișcă, Dragoș Florea, Manuela Nica, Eliza Manea, Simona Merișor, Cristian M Nicolae, Simin A Florescu, Irina M Dumitru, Emanoil Ceaușu, Sorin Rugină, Ruxandra V Moroti A102 Knowledge, risk perception and attitudes of healthcare workers at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” regarding Ebola Daniela Pițigoi, Teodora Ionescu, Oana Săndulescu, Maria Nițescu, Bogdan Nițescu, Iulia Monica Mustaţă, Sorina Claudia Boldeanu, Florentina Furtunescu, Adrian Streinu-Cercel A103 A case of abdominopelvic actinomycosis with successful short-term antibiotic treatment Diana Gabriela Iacob, Simona Alexandra Iacob, Mihaela Gheorghe A104 A case of pneumonia caused by Raoultella planticola Iulian Diaconescu, Irina Niculescu, Floretina Dumitrescu, Lucian Giubelan A105 Vitamin D deficiency and sepsis in childhood Adriana Slavcovici, Raluca Tripon, Roxana Iubu, Cristian Marcu, Mihaela Sabou, Monica Muntean A106 The clinical and epidemiological aspects and prophylaxis of Lyme disease among patients who presented with tick bites to the Clinical Infectious Disease Hospital “Toma Ciorbă” Ion Chiriac, Tiberiu Holban, Liviu Tazlavanu A107 Drug-resistant tuberculosis in HIV infected patients Raluca Jipa, Eliza Manea, Roxana Cernat, Kezdi Iringo, Andrei Vâță, Manuela Arbune, Teodora Moisil, Adriana Hristea A108 Kidney injury molecule-1 and urinary tract infections Corina-Daniela Ene, Ilinca Nicolae, Roxana Simona Georgescu A109 The impact of microbiological agents on serum gangliosides in patients with benign prostate hyperplasia Corina-Daniela Ene, Cosmin-Victor Ene, Roxana Simona Georgescu, Marilena Ciortea , Lucreția Dulgheru, Ilinca Nicolae A110 Toxocariasis - the experience of the Iași Infectious Diseases Hospital between 2013–2015 Mihaela Cătălina Luca, Ioana-Alina Harja-Alexa, Roxana Nemescu, Mădălina Popazu, Andrei Ștefan Luca A111 Species of anaerobic Gram-positive cocci involved in odontogenic abscesses Gabriela Bancescu, Bogdan Dabu, Adrian Bancescu A112 Clostridium difficile infection recurrences Eliza Manea, Raluca Jipa, Adriana Hristea A113 Differential diagnosis of staphylococcal and tuberculous osteodiscitis – case report Adina Elena Ilie, Săftica-Mariana Pohrib, Alina Cristina Neguț, Maria-Sabina Tache, Maria Magdalena Moțoi, Oana Săndulescu, Ion Aurel Iliescu, Adrian Streinu-Cercel A114 Severe clinical forms of respiratory syncytial virus infections Cristina Tecu, Maria-Elena Mihai, Mihaela Lazăr, Carmen Cherciu, Alina Ivanciuc, Daniela Pițigoi, Emilia Lupulescu A115 Acinetobacter baumannii postoperative sepsis associated with Clostridium difficile enterocolitis in an immune suppressed elderly patient Mirela Paliu, Manuela Curescu, Bianca Cerbu, Iosif Marincu A116 Risk factors and their impact on psychopathology and quality of life among people living with HIV/AIDS in Romania Fulvia Ursoiu, Mirandolina Prișcă, George Ciprian Pribac A117 Antivirals susceptibility of influenza viruses circulating in Romania Maria Elena Mihai, Carmen Maria Cherciu, Alina Elena Ivanciuc, Cristina Tecu, Emilia Lupulescu A118 Retrospective study of hospitalized cases of sepsis at the Hospital Clinic of Infectious Diseases “Toma Ciorbă” Irina Bunescu, Tiberiu Holban, Ana Pasnin, Stela Semeniuc, Raisa Popovici, Galina Chiriacov
Published: 2016
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46. Usefulness and safety from stereotactic biopsy in posterior fossa lesions in adult patients

Author: Sergio, Moreno-Jiménez, Néstor, Martínez-Vaca, Bárbara, Pérez-Aguilar, Brenda, Gómez-Calva, Jorge J, Díaz-Chávez, and Michel G, Mondragón-Soto
Subjects: Adult, Aged, 80 and over, Male, Brain Diseases, Adolescent, Biopsy, Supratentorial Neoplasms, Infratentorial Neoplasms, Glioma, Meningitis, Cryptococcal, Middle Aged, Stereotaxic Techniques, Young Adult, Humans, Female, Gliosis, Intracranial Hemorrhages, Aged, Retrospective Studies
Abstract: Stereotactic biopsy has been reported as a useful and safety procedure in pediatric patients. In adult patients exist more controversy because a greater number of diagnostic options.To demonstrate its usefulness and safety in adult patients with posterior fossa pathology.From 2006-2014, 23 patients were operated from posterior fossa. Variables: age, gender, state, pre- and postoperative diagnosis, stereotactic device, location and complications.52.2% females and 47.8% males. The location was ponto-mesencephalic 43.5%, cerebellum 39.1%, bulbar 13% and pineal region 4.3%. The preoperative diagnosis was brainstem glioma 78.2%, lymphoma 8.7%, and meningioma, metastasis and abscess 4.3% each one. In 73.9% Zamorano-Dujovni device was used and in 26.1% the CRW. The definitive diagnosis was pilocytic astrocytoma 17.4%, diffuse astrocytoma 13%, inflammatory response 13%, anaplastic astrocytoma 8.7%, gliosis 8.7%, glioblastoma, neuroectodermic primitive tumor, germinoma, pineocytoma and cryptococcosis 4.3% each one. In 17.4% there was no diagnosis. The preoperative diagnosis was concordant in 43.5%. One transient deficit and one pin displacement 4.3% were present. 91.4% without complications.It is a useful, necessary and safety procedure in adult patients.La biopsia por estereotaxia ha sido reportada como segura y útil en pediatría. En adultos es más controvertida debido a la mayor diversidad de opciones diagnósticas.Demostrar su utilidad y seguridad en pacientes adultos con patología de fosa posterior.En 2006-2014 se operaron 23 pacientes de fosa posterior. Variables: edad, sexo, diagnóstico preoperatorio y posoperatorio, estereotáctico, localización y complicaciones.52.2% mujeres y 47.8% hombres. La localización fue la región pontomesencefálica en el 43.5%, el cerebelo en el 39.1%, bulbar en el 13% y pineal en el 4.3%. El diagnóstico preoperatorio fue glioma de tallo en el 78.2%, linfoma en el 8.7% y meningioma, metástasis y absceso en el 4.3% cada uno. En el 73.9% se utilizó el sistema Zamorano-Dujovni y en el 26.1% el CRW. El diagnóstico definitivo fue astrocitoma pilocítico en el 17.4%, astrocitoma difuso en el 13%, respuesta inflamatoria en el 13%, astrocitoma anaplásico en el 8.7%, gliosis en el 8.7%, y glioblastoma, tumor neuroectodérmico primitivo, germinoma, pineoctioma y criptococosis en el 4.3% cada uno. En el 17.4% no hubo diagnóstico. El diagnóstico preoperatorio fue concordante en el 43.5%. Hubo un déficit transitorio y un desplazamiento de uno de los pinchos en el 4.3% de los casos. En el 91.4% no hubo complicaciones.Es un procedimiento útil, necesario y seguro en pacientes adultos.
Published: 2019

47. Biological insights into multiple birth: genetic findings from UK Biobank

Author: Margot P van de Weijer, Erik A. Ehli, Michel G. Nivard, Jeffrey J. Beck, Gareth E. Davies, Mathijs D van der Zee, A. Abdellaoui, Hamdi Mbarek, Eco J. C. de Geus, Hill F. Ip, Dorret I. Boomsma, Bart M. L. Baselmans, Meike Bartels, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Methodology, and Adult Psychiatry
Subjects: Adult, Male, Netherlands Twin Register (NTR), media_common.quotation_subject, Dizygotic twin, Genome-wide association study, Fertility, Biology, Multiple Birth Offspring, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetics, Genetic predisposition, Twins, Dizygotic, Humans, Genetics (clinical), media_common, Aged, Biological Specimen Banks, Aged, 80 and over, 0303 health sciences, 030305 genetics & heredity, Twins, Monozygotic, Middle Aged, Twin study, Biobank, Protein Inhibitors of Activated STAT, United Kingdom, Trait, Small Ubiquitin-Related Modifier Proteins, Multiple birth, Female, Co-Repressor Proteins, Genome-Wide Association Study
Abstract: The tendency to conceive spontaneous dizygotic (DZ) twins is a complex trait with important contributions from both environmental factors and genetic disposition. In earlier work, we identified the first two genes as maternal susceptibility loci for DZ twinning. The aim of this study was to identify genetic variants influencing multiple births and to genetically correlate the findings across a broad range of traits. We performed a genome-wide association study (GWAS) in 8962 participants with Caucasian ancestry from UK Biobank who reported being part of a multiple birth, and 409,591 singleton controls. We replicated the association between FSHB, SMAD3 and twinning in the gene-based (but not SNP-based) test, which had been established in previous genome-wide association analyses in mothers with dizygotic twin offspring. Additionally, we report a novel genetic variant associated with multiple birth, rs428022 at 15q23 (p = 2.84 × 10-8) close to two genes: PIAS1 and SKOR1. Finally, we identified meaningful genetic correlations between being part of a multiple birth and other phenotypes (anthropometric traits, health-related traits, and fertility-related measures). The outcomes of this study provide important new insights into the genetic aetiology of multiple births and fertility, and open up novel directions for fertility and reproduction research.
Published: 2019

48. A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms

Author: René Pool, Sabine Spijker, T. E. Galesloot, Josep Antoni Ramos-Quiroga, Barbara Franke, Jan K. Buitelaar, Marieke Klein, Catharina A. Hartman, Janita Bralten, Christel M. Middeldorp, Michel G. Nivard, Conor V. Dolan, Dina Vojinovic, Lambertus A. Kiemeney, Ilja M. Nolte, Najaf Amin, Alexander J. Groffen, V. M. Kattenberg, Alejandro Arias-Vasquez, A. den Braber, Cristina Sánchez-Mora, Iryna O. Fedko, J.J.S. Kooij, J-J Hottenga, Sita H. Vermeulen, August B. Smit, Klaasjan G. Ouwens, Dorret I. Boomsma, Martine Hoogman, C.M. van Duijn, Pieter J. Hoekstra, Harmen H.M. Draisma, Marta Ribasés, Brenda W.J.H. Penninx, P. J. van der Most, Human genetics, APH - Mental Health, Psychiatry, Neurology, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, APH - Health Behaviors & Chronic Diseases, APH - Digital Health, Epidemiology, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Functional Genomics, Molecular and Cellular Neurobiology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, APH - Personalized Medicine, APH - Methodology, EMGO+ - Lifestyle, Overweight and Diabetes, Center for Neurogenomics and Cognitive Research, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Male, 0301 basic medicine, Oncology, Netherlands Twin Register (NTR), Genome-wide association study, TOMOSYN, Cohort Studies, R-SNARE Proteins, Mice, 0302 clinical medicine, Risk Factors, Epidemiology, GWAS, Prefrontal cortex, Genetics (clinical), education.field_of_study, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, ASSOCIATION, Phenotype, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Female, RNA, Long Noncoding, medicine.symptom, SNARE COMPLEX, Adult, medicine.medical_specialty, Genotype, Population, Nerve Tissue Proteins, Single-nucleotide polymorphism, Impulsivity, BIOBANK, Polymorphism, Single Nucleotide, ADHD symptoms, DNA, Antisense, ENVIRONMENTAL-INFLUENCES, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Internal medicine, Genetics, medicine, Animals, Humans, SNP, Adults, Genetic Predisposition to Disease, AUTISM, education, Ecology, Evolution, Behavior and Systematics, DEFICIT-HYPERACTIVITY-DISORDER, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Heritability, STXBP5-AS1 gene, Genetics, Population, HEK293 Cells, 030104 developmental biology, Attention Deficit Disorder with Hyperactivity, RNA, SCALES, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 individuals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753; p-value = 3.02 × 10 −7 ) was present in the long non-coding RNA gene STXBP5-AS1. This association was also observed in a meta-analysis of childhood ADHD symptom scores in eight population-based pediatric cohorts from the Early Genetics and Lifecourse Epidemiology (EAGLE) ADHD consortium (n = 14,776). Genome-wide meta-analysis of the SAGA and EAGLE data (n = 29,465) increased the strength of the association with the SNP rs12661753. In human HEK293 cells, expression of STXBP5-AS1 enhanced the expression of a reporter construct of STXBP5, a gene known to be involved in “SNAP” (Soluble NSF attachment protein) Receptor” (SNARE) complex formation. In mouse strains featuring different levels of impulsivity, transcript levels in the prefrontal cortex of the mouse ortholog Gm28905 strongly correlated negatively with motor impulsivity as measured in the five choice serial reaction time task (r 2 = − 0.61; p = 0.004). Our results are consistent with an effect of the STXBP5-AS1 gene on ADHD symptom scores distribution and point to a possible biological mechanism, other than antisense RNA inhibition, involved in ADHD-related impulsivity levels.
Published: 2019

49. A Genetic Investigation of the Well-Being Spectrum

Author: Bart M. L. Baselmans, Gonneke Willemsen, M. P. van de Weijer, E.J.C. de Geus, Abdel Abdellaoui, J-J Hottenga, Jacqueline M. Vink, Michel G. Nivard, Dorret I. Boomsma, Meike Bartels, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, and APH - Methodology
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), Multifactorial Inheritance, congenital, hereditary, and neonatal diseases and abnormalities, Genetic correlation, Neuropsychological Tests, Factor structure, Spectrum (topology), Extraversion, Psychological, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Self-rated health, Statistics, Genetics, medicine, Humans, cardiovascular diseases, Big Five personality traits, Life Style, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Genetic Association Studies, Original Research, Neuroticism, Extraversion and introversion, Depression, Loneliness, Correction, Flourishing, Regression, 030104 developmental biology, Phenotype, Well-being, Quality of Life, Female, medicine.symptom, Well-being spectrum, Psychology, Developmental Psychopathology, 030217 neurology & neurosurgery, Personality
Abstract: The interrelations among well-being, neuroticism, and depression can be captured in a so-called well-being spectrum (3-phenotype well-being spectrum, 3-WBS). Several other human traits are likely linked to the 3-WBS. In the present study, we investigate how the 3-WBS can be expanded. First, we constructed polygenic risk scores for the 3-WBS and used this score to predict a series of traits that have been associated with well-being in the literature. We included information on loneliness, big five personality traits, self-rated health, and flourishing. The 3-WBS polygenic score predicted all the original 3-WBS traits and additionally loneliness, self-rated health, and extraversion (R2 between 0.62% and 1.58%). Next, using LD score regression, we calculated genetic correlations between the 3-WBS and the traits of interest. From all candidate traits, loneliness and self-rated health were found to have the strongest genetic correlations (rg = − 0.79, and rg= 0.64, respectively) with the 3-WBS. Lastly, we use Genomic SEM to investigate the factor structure of the proposed spectrum. The best model fit was obtained for a two-factor model including the 5-WBS traits, with two highly correlated factors representing the negative- and positive end of the spectrum. Based on these analyses we propose to include loneliness and self-rated health in the WBS and use a 5-phenotype well-being spectrum in future studies to gain more insight into the determinants of human well-being. Electronic supplementary material The online version of this article (10.1007/s10519-019-09951-0) contains supplementary material, which is available to authorized users.
Published: 2019

50. Risk factors affecting outcome of unrelated cord blood transplantation for children with familial haemophagocytic lymphohistiocytosis

Author: Furtado-Silva, J.M., Paviglianili, A., Ruggeri, A., Boelens, J.J., Veys, P., Ahmari, A.A., Zecca, M., Locatelli, F., Michel, G., Volt, F., Kenzey, C., Sedlacek, P., Rao, K., Lankester, A., Gluckman, E., Rocha, V., Eurocord Monacord Cord Blood Comm, and European Blood Marrow Transplant
Subjects: Male, medicine.medical_specialty, Transplantation Conditioning, Adolescent, Cord Blood Stem Cell Transplantation, familial haemophagocytic lymphohistiocytosis, paediatric, transplant outcomes, umbilical cord blood transplantation, unrelated donor, Gastroenterology, Disease-Free Survival, Lymphohistiocytosis, Hemophagocytic, Familial haemophagocytic lymphohistiocytosis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Humans, Cumulative incidence, Child, Survival rate, Retrospective Studies, Umbilical cord blood transplantation, Neutrophil Engraftment, business.industry, Umbilical Cord Blood Transplantation, Infant, Newborn, Infant, Hematology, Allografts, Transplantation, Survival Rate, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Paediatric, 030220 oncology & carcinogenesis, Child, Preschool, Alemtuzumab, Female, business, Unrelated Donors, 030215 immunology, medicine.drug
Abstract: Allogeneic haematopoietic stem cell transplantation is still the only available curative option for Familial Haemophagocytic Lymphohistiocytosis (FHLH). Most studies report outcomes after bone marrow or peripheral blood stem cell transplantation. We analysed the outcomes of 118 children with FHLH undergoing single-unit umbilical cord blood transplantation performed from 1996 to 2014. Myeloablative conditioning regimen was given to 90% of the patients, and was mostly busulfan-based (n = 81, 76%), including anti-thymocyte globulin or alemtuzumab (n = 102, 86%). The cumulative incidence of Day 60 neutrophil engraftment was 85%; and that of non-relapse mortality and acute graft-versus-host disease (GvHD) was 21% and 33% at 100 days, respectively. The 6-year cumulative incidence of chronic GvHD was 17% and the 6-year probability of overall survival was 55%. In multivariate analysis, children receiving a graft with a total nucleated cell dose greater than 9·9 × 107 /kg had a better overall survival (hazard ratio [HR]: 0·49, 95% CI: 0·27-0·88, P = 0·02). Degree of human leucocyte antigen (HLA) matching was associated with improved disease-free survival (5/6 vs. 6/6 HR: 2·11, 95% confidence interval [CI]: 1·01-4·4, P = 0·05 and ≤4/6 vs. 6/6, HR: 2·82, CI: 1·27-6·23, P = 0·01). Umbilical cord blood transplantation with a high cell dose and good HLA match is a suitable alternative option to haematopoietic stem cell transplantation in children with FHLH who lack a HLA-matched donor.
Published: 2019

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