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https://read.qxmd.com/read/30755487/epilepsy-gene-therapy-using-an-engineered-potassium-channel
#1
Albert Snowball, Elodie Chabrol, Robert C Wykes, Tawfeeq Shekh-Ahmad, Jonathan H Cornford, Andreas Lieb, Michael P Hughes, Giulia Massaro, Ahad A Rahim, Kevan S Hashemi, Dimitri M Kullmann, Matthew C Walker, Stephanie Schorge
Refractory focal epilepsy is a devastating disease for which there is frequently no effective treatment. Gene therapy represents a promising alternative, but treating epilepsy in this way involves irreversible changes to brain tissue, so vector design must be carefully optimized to guarantee safety without compromising efficacy. We set out to develop an epilepsy gene therapy vector optimized for clinical translation. The gene encoding the voltage-gated potassium channel Kv1.1, KCNA1 , was codon-optimized for human expression and mutated to accelerate the channels' recovery from inactivation...
February 12, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://read.qxmd.com/read/30715555/delayed-tine-displacement-of-a-casper-carotid-artery-stent-due-to-styloid-process-compression
#2
Daren Tan, Matthew Thomas Crockett, Albert Ho Yuen Chiu
No abstract text is available yet for this article.
February 4, 2019: Clinical Neuroradiology
https://read.qxmd.com/read/30715542/from-computation-to-the-first-person-auditory-verbal-hallucinations-and-delusions-of-thought-interference-in-schizophrenia-spectrum-psychoses
#3
Clara S Humpston, Rick A Adams, David Benrimoh, Matthew R Broome, Philip R Corlett, Philip Gerrans, Guillermo Horga, Thomas Parr, Elizabeth Pienkos, Albert R Powers, Andrea Raballo, Cherise Rosen, David E J Linden
Schizophrenia-spectrum psychoses are highly complex and heterogeneous disorders that necessitate multiple lines of scientific inquiry and levels of explanation. In recent years, both computational and phenomenological approaches to the understanding of mental illness have received much interest, and significant progress has been made in both fields. However, there has been relatively little progress bridging investigations in these seemingly disparate fields. In this conceptual review and collaborative project from the 4th Meeting of the International Consortium on Hallucination Research, we aim to facilitate the beginning of such dialogue between fields and put forward the argument that computational psychiatry and phenomenology can in fact inform each other, rather than being viewed as isolated or even incompatible approaches...
February 1, 2019: Schizophrenia Bulletin
https://read.qxmd.com/read/30712868/limbic-neurons-shape-sex-recognition-and-social-behavior-in-sexually-naive-males
#4
Daniel W Bayless, Taehong Yang, Matthew M Mason, Albert A T Susanto, Alexandra Lobdell, Nirao M Shah
Sexually naive animals have to distinguish between the sexes because they show species-typical interactions with males and females without meaningful prior experience. However, central neural pathways in naive mammals that recognize sex of other individuals remain poorly characterized. We examined the role of the principal component of the bed nucleus of stria terminalis (BNSTpr), a limbic center, in social interactions in mice. We find that activity of aromatase-expressing BNSTpr (AB) neurons appears to encode sex of other animals and subsequent displays of mating in sexually naive males...
January 24, 2019: Cell
https://read.qxmd.com/read/30700444/elevated-platelet-count-appears-to-be-causally-associated-with-increased-risk-of-lung-cancer-a-mendelian-randomization-analysis
#5
Ying Zhu, Yongyue Wei, Ruyang Zhang, Xuesi Dong, Sipeng Shen, Yang Zhao, Jianling Bai, Demetrius Albanes, Neil E Caporaso, Maria Teresa Landi, Bin Zhu, Stephen J Chanock, Fangyi Gu, Stephen Lam, Ming-Sound Tsao, Frances A Shepherd, Adonina Tardon, Ana Fernández-Somoano, Guillermo Fernandez-Tardon, Chu Chen, Matthew J Barnett, Jennifer Doherty, Stig E Bojesen, Mattias Johansson, Paul Brennan, James D McKay, Robert Carreras-Torres, Thomas Muley, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboeller, Albert Rosenberger, Gad Rennert, Walid Saliba, Susanne M Arnold, John K Field, Michael P A Davies, Michael W Marcus, Xifeng Wu, Yuanqing Ye, Loic Le Marchand, Lynne R Wilkens, Olle Melander, Jonas Manjer, Hans Brunnström, Rayjean J Hung, Geoffrey Liu, Yonathan Brhane, Linda Kachuri, Angeline S Andrew, Eric J Duell, Lambertus A Kiemeney, Erik H F M van der Heijden, Aage Haugen, Shanbeh Zienolddiny, Vidar Skaug, Kjell Grankvist, Mikael Johansson, Penella J Woll, Angela Cox, Fiona Taylor, Dawn M Teare, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Richard S Houlston, John McLaughlin, Victoria L Stevens, Hongbing Shen, Zhibin Hu, Juncheng Dai, Christopher I Amos, Younghun Han, Dakai Zhu, Gary E Goodman, Feng Chen, David C Christiani
BACKGROUND: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. METHODS: We performed single and combined multiple instrumental variable Mendelian Randomization(MR) analysis by an inverse-weighted (IVW) method, in addition to a series of sensitivity analyses. Summary data for associations between single nucleotide polymorphisms (SNPs) and platelet count is from a recent publication including 48,666 Caucasian Europeans and International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls analyze associations between candidate single nucleotide polymorphisms and lung cancer risk...
January 30, 2019: Cancer Epidemiology, Biomarkers & Prevention
https://read.qxmd.com/read/30688816/postoperative-changes-in-orbital-dysmorphology-in-patients-with-unicoronal-synostosis
#6
Leahthan F Domeshek, Albert Woo, Gary B Skolnick, Sybill Naidoo, David Segar, Matthew Smyth, Mark Proctor, Kamlesh B Patel
Orbital asymmetry in unicoronal synostosis impacts craniofacial appearance and can potentiate functional visual disturbances, such as strabismus. Surgical treatment aims to normalize overall cranial morphology, including that of the orbits. The purpose of this study was to compare postoperative changes in orbital asymmetry following 2 common procedures.Preoperative and 1-year postoperative computed tomography scans for patients with isolated, nonsyndromic unicoronal synostosis treated from 2007 to 2012, at 2 academic institutions were analyzed...
January 23, 2019: Journal of Craniofacial Surgery
https://read.qxmd.com/read/30679315/a-phase-ii-randomized-trial-of-panitumumab-erlotinib-and-gemcitabine-versus-erlotinib-and-gemcitabine-in-patients-with-untreated-metastatic-pancreatic-adenocarcinoma-north-central-cancer-treatment-group-trial-n064b-alliance
#7
Thorvardur R Halfdanarson, Nathan R Foster, George P Kim, Jeffrey P Meyers, Thomas C Smyrk, Ann E McCullough, Matthew M Ames, Jeffrry P Jaffe, Steven R Alberts
LESSONS LEARNED: Dual epidermal growth factor receptor (EGFR)-directed therapy with erlotinib and panitumumab in combination with gemcitabine was superior to gemcitabine and erlotinib, but the clinical relevance is uncertain given the limited role of gemcitabine monotherapy.A significantly longer overall survival was observed in patients receiving the dual EGFR-directed therapy.The dual EGFR-directed therapy resulted in increased toxicity. BACKGROUND: Gemcitabine is active in patients with advanced pancreatic adenocarcinoma...
January 24, 2019: Oncologist
https://read.qxmd.com/read/30664687/klf9-dependent-ros-regulate-melanoma-progression-in-stage-specific-manner
#8
Archis Bagati, Sudha Moparthy, Emily E Fink, Anna Bianchi-Smiraglia, Dong Hyun Yun, Masha Kolesnikova, Olga O Udartseva, David W Wolff, Matthew V Roll, Brittany C Lipchick, Zhannan Han, Nadezhda I Kozlova, Peter Jowdy, Albert E Berman, Neil F Box, Cesar Rodriguez, Wiam Bshara, Eugene S Kandel, Maria S Soengas, Gyorgy Paragh, Mikhail A Nikiforov
Although antioxidants promote melanoma metastasis, the role of reactive oxygen species (ROS) in other stages of melanoma progression is controversial. Moreover, genes regulating ROS have not been functionally characterized throughout the entire tumor progression in mouse models of cancer. To address this question, we crossed mice-bearing knock-out of Klf9, an ubiquitous transcriptional regulator of oxidative stress, with two conditional melanocytic mouse models: BrafCA mice, where BrafV600E causes premalignant melanocytic hyperplasia, and BrafCA /Pten-/- mice, where BrafV600E and loss of Pten induce primary melanomas and metastases...
January 21, 2019: Oncogene
https://read.qxmd.com/read/30651383/genetic-and-lifestyle-risk-factors-for-mri-defined-brain-infarcts-in-a-population-based-setting
#9
Ganesh Chauhan, Hieab H H Adams, Claudia L Satizabal, Joshua C Bis, Alexander Teumer, Muralidharan Sargurupremraj, Edith Hofer, Stella Trompet, Saima Hilal, Albert Vernon Smith, Xueqiu Jian, Rainer Malik, Matthew Traylor, Sara L Pulit, Philippe Amouyel, Bernard Mazoyer, Yi-Cheng Zhu, Sara Kaffashian, Sabrina Schilling, Gary W Beecham, Thomas J Montine, Gerard D Schellenberg, Olafur Kjartansson, Vilmundur Guðnason, David S Knopman, Michael E Griswold, B Gwen Windham, Rebecca F Gottesman, Thomas H Mosley, Reinhold Schmidt, Yasaman Saba, Helena Schmidt, Fumihiko Takeuchi, Shuhei Yamaguchi, Toru Nabika, Norihiro Kato, Kumar B Rajan, Neelum T Aggarwal, Philip L De Jager, Denis A Evans, Bruce M Psaty, Jerome I Rotter, Kenneth Rice, Oscar L Lopez, Jiemin Liao, Christopher Chen, Ching-Yu Cheng, Tien Y Wong, Mohammad K Ikram, Sven J van der Lee, Najaf Amin, Vincent Chouraki, Anita L DeStefano, Hugo J Aparicio, Jose R Romero, Pauline Maillard, Charles DeCarli, Joanna M Wardlaw, Maria Del C Valdés Hernández, Michelle Luciano, David Liewald, Ian J Deary, John M Starr, Mark E Bastin, Susana Muñoz Maniega, P Eline Slagboom, Marian Beekman, Joris Deelen, Hae-Won Uh, Robin Lemmens, Henry Brodaty, Margaret J Wright, David Ames, Giorgio B Boncoraglio, Jemma C Hopewell, Ashley H Beecham, Susan H Blanton, Clinton B Wright, Ralph L Sacco, Wei Wen, Anbupalam Thalamuthu, Nicola J Armstrong, Elizabeth Chong, Peter R Schofield, John B Kwok, Jeroen van der Grond, David J Stott, Ian Ford, J Wouter Jukema, Meike W Vernooij, Albert Hofman, André G Uitterlinden, Aad van der Lugt, Katharina Wittfeld, Hans J Grabe, Norbert Hosten, Bettina von Sarnowski, Uwe Völker, Christopher Levi, Jordi Jimenez-Conde, Pankaj Sharma, Cathie L M Sudlow, Jonathan Rosand, Daniel Woo, John W Cole, James F Meschia, Agnieszka Slowik, Vincent Thijs, Arne Lindgren, Olle Melander, Raji P Grewal, Tatjana Rundek, Kathy Rexrode, Peter M Rothwell, Donna K Arnett, Christina Jern, Julie A Johnson, Oscar R Benavente, Sylvia Wasssertheil-Smoller, Jin-Moo Lee, Quenna Wong, Braxton D Mitchell, Stephen S Rich, Patrick F McArdle, Mirjam I Geerlings, Yolanda van der Graaf, Paul I W de Bakker, Folkert W Asselbergs, Velandai Srikanth, Russell Thomson, Rebekah McWhirter, Chris Moran, Michele Callisaya, Thanh Phan, Loes C A Rutten-Jacobs, Steve Bevan, Christophe Tzourio, Karen A Mather, Perminder S Sachdev, Cornelia M van Duijn, Bradford B Worrall, Martin Dichgans, Steven J Kittner, Hugh S Markus, Mohammad A Ikram, Myriam Fornage, Lenore J Launer, Sudha Seshadri, W T Longstreth, Stéphanie Debette
OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI...
January 16, 2019: Neurology
https://read.qxmd.com/read/30643258/genome-wide-association-analyses-of-risk-tolerance-and-risky-behaviors-in-over-1-million-individuals-identify-hundreds-of-loci-and-shared-genetic-influences
#10
Richard Karlsson Linnér, Pietro Biroli, Edward Kong, S Fleur W Meddens, Robbee Wedow, Mark Alan Fontana, Maël Lebreton, Stephen P Tino, Abdel Abdellaoui, Anke R Hammerschlag, Michel G Nivard, Aysu Okbay, Cornelius A Rietveld, Pascal N Timshel, Maciej Trzaskowski, Ronald de Vlaming, Christian L Zünd, Yanchun Bao, Laura Buzdugan, Ann H Caplin, Chia-Yen Chen, Peter Eibich, Pierre Fontanillas, Juan R Gonzalez, Peter K Joshi, Ville Karhunen, Aaron Kleinman, Remy Z Levin, Christina M Lill, Gerardus A Meddens, Gerard Muntané, Sandra Sanchez-Roige, Frank J van Rooij, Erdogan Taskesen, Yang Wu, Futao Zhang, Adam Auton, Jason D Boardman, David W Clark, Andrew Conlin, Conor C Dolan, Urs Fischbacher, Patrick J F Groenen, Kathleen Mullan Harris, Gregor Hasler, Albert Hofman, Mohammad A Ikram, Sonia Jain, Robert Karlsson, Ronald C Kessler, Maarten Kooyman, James MacKillop, Minna Männikkö, Carlos Morcillo-Suarez, Matthew B McQueen, Klaus M Schmidt, Melissa C Smart, Matthias Sutter, A Roy Thurik, André G Uitterlinden, Jon White, Harriet de Wit, Jian Yang, Lars Bertram, Dorret I Boomsma, Tõnu Esko, Ernst Fehr, David A Hinds, Magnus Johannesson, Meena Kumari, David Laibson, Patrik K E Magnusson, Michelle N Meyer, Arcadi Navarro, Abraham A Palmer, Tune H Pers, Danielle Posthuma, Daniel Schunk, Murray B Stein, Rauli Svento, Henning Tiemeier, Paul R H J Timmers, Patrick Turley, Robert J Ursano, Gert G Wagner, James F Wilson, Jacob Gratten, James J Lee, David Cesarini, Daniel J Benjamin, Philipp D Koellinger, Jonathan P Beauchamp
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...
January 14, 2019: Nature Genetics
https://read.qxmd.com/read/30606238/circadian-oscillations-of-cytosine-modification-in-humans-contribute-to-epigenetic-variability-aging-and-complex-disease
#11
Gabriel Oh, Karolis Koncevičius, Sasha Ebrahimi, Matthew Carlucci, Daniel Erik Groot, Akhil Nair, Aiping Zhang, Algimantas Kriščiūnas, Edward S Oh, Viviane Labrie, Albert H C Wong, Juozas Gordevičius, Peixin Jia, Miki Susic, Art Petronis
BACKGROUND: Maintenance of physiological circadian rhythm plays a crucial role in human health. Numerous studies have shown that disruption of circadian rhythm may increase risk for malignant, psychiatric, metabolic, and other diseases. RESULTS: Extending our recent findings of oscillating cytosine modifications (osc-modCs) in mice, in this study, we show that osc-modCs are also prevalent in human neutrophils. Osc-modCs may play a role in gene regulation, can explain parts of intra- and inter-individual epigenetic variation, and are signatures of aging...
January 3, 2019: Genome Biology
https://read.qxmd.com/read/30598050/conscious-sedation-for-pediatric-peritonsillar-abscess-comparison-of-anesthetic-approaches
#12
M Elise Graham, Abigail K Neal, Ian C Newberry, Matthew A Firpo, Albert H Park
OBJECTIVE: To compare the efficacy, safety, and cost of incision and drainage (I&D) for pediatric patients with peritonsillar abscesses (PTAs) under conscious sedation (CS) versus unsedated (awake) and general anesthesia (GA). STUDY DESIGN: Case series with chart review. SETTING: Tertiary pediatric hospital. SUBJECTS AND METHODS: Records for all pediatric patients (<18 years) treated for PTAs in the emergency department from 2005 to 2015 were reviewed and stratified into awake, CS, and GA groups for comparison...
January 1, 2019: Otolaryngology—Head and Neck Surgery
https://read.qxmd.com/read/30594876/long-term-trajectories-of-depressive-symptoms-in-old-age-relationships-with-sociodemographic-and-health-related-factors
#13
Alejandro de la Torre-Luque, Javier de la Fuente, Matthew Prina, Albert Sanchez-Niubo, Josep Maria Haro, Jose Luis Ayuso-Mateos
BACKGROUND: This study aimed at depicting the course of depression symptoms over the old age, with a special interest in a) uncovering its relationships with sociodemographic and health-related factors; b) analysing its predictive role on healthy-ageing outcomes later in life. METHODS: The sample comprised 8317 older adults (46.02% men) from the English Longitudinal Study of Ageing. Robust structural equation modelling was used to identify symptom trajectories and their relationships with time-varying factors...
December 25, 2018: Journal of Affective Disorders
https://read.qxmd.com/read/30584580/clinical-differences-in-copd-patients-with-variable-patterns-of-hypoxemia
#14
Erin R Narewski, Amanda L Blackford, Matthew R Lammi, Anne L Fuhlbrigge, Xavier Soler, Richard Albert, Gerard J Criner
Background: Chronic obstructive pulmonary disease (COPD) patients enrolled into the Long-term Oxygen Treatment Trial had hypoxemia at rest, hypoxemia on exertion, or hypoxemia both at rest and on exertion. We hypothesized that patients with different patterns of hypoxemia may have significant differences in clinical features. Methods: All patients had COPD and oxygen saturation measured by pulse oximetry (blood oxygenation [SpO2 ]) at rest and during the 6-minute walk test (6MWT). Hypoxemia at rest was defined as resting SpO2 between 89-93%...
April 28, 2018: Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation
https://read.qxmd.com/read/30574493/the-use-of-intravitreal-anti-vegf-and-triamcinolone-in-the-treatment-of-radiation-papillopathy
#15
Kelsey Roelofs, Matthew P Larocque, Albert Murtha, Ezekiel Weis
Background/Aims: To evaluate a treatment regimen for radiation papillopathy. Methods: This is a prospective noncomparative interventional case series of patients who developed radiation papillopathy after plaque brachytherapy for uveal melanoma. Treatment consisted of intravitreal bevacizumab (IVB) (1.25 mg in 0.05 mL) at the time of diagnosis, and 1 week later, intravitreal triamcinolone (IVK) (2.00 mg in 0.05 mL). One month later, patients again received both IVB and IVK...
November 2018: Ocular Oncology and Pathology
https://read.qxmd.com/read/30571498/machine-learning-outperforms-acc-aha-cvd-risk-calculator-in-mesa
#16
Ioannis A Kakadiaris, Michalis Vrigkas, Albert A Yen, Tatiana Kuznetsova, Matthew Budoff, Morteza Naghavi
Background Studies have demonstrated that the current US guidelines based on American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equations Risk Calculator may underestimate risk of atherosclerotic cardiovascular disease ( CVD ) in certain high-risk individuals, therefore missing opportunities for intensive therapy and preventing CVD events. Similarly, the guidelines may overestimate risk in low risk populations resulting in unnecessary statin therapy. We used Machine Learning ( ML ) to tackle this problem...
November 20, 2018: Journal of the American Heart Association
https://read.qxmd.com/read/30570141/new-tools-for-pathology-a-user-s-review-of-a-highly-multiplexed-method-for-in-situ-analysis-of-protein-and-rna-expression-in-tissue
#17
REVIEW
Jérémie Decalf, Matthew L Albert, James Ziai
Tumor cell heterogeneity and tumor cell - stromal interactions are being explored as determinants of disease progression and treatment resistance in solid tumor and hematologic malignancies. As such, tools simultaneously capable of highly-multiplexed profiling of tissues' protein and RNA content, as well as interrogation of rare or single cells, are required to precisely characterize constituent tumor cell populations, infiltrating lymphocytes and stromal elements. Access to spatial relationships will enable more precise characterization of tumors, support patient stratification and may help to identify novel drug targets...
December 20, 2018: Journal of Pathology
https://read.qxmd.com/read/30517875/integrated-in-vivo-quantitative-proteomics-and-nutrient-tracing-reveals-age-related-metabolic-rewiring-of-pancreatic-%C3%AE-cell-function
#18
Matthew Wortham, Jacqueline R Benthuysen, Martina Wallace, Jeffrey N Savas, Francesca Mulas, Ajit S Divakaruni, Fenfen Liu, Verena Albert, Brandon L Taylor, Yinghui Sui, Enrique Saez, Anne N Murphy, John R Yates, Christian M Metallo, Maike Sander
Pancreatic β cell physiology changes substantially throughout life, yet the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivo quantitative proteomic profiling of pancreatic islets from juvenile and 1-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion...
December 4, 2018: Cell Reports
https://read.qxmd.com/read/30510157/gwas-and-colocalization-analyses-implicate-carotid-intima-media-thickness-and-carotid-plaque-loci-in-cardiovascular-outcomes
#19
Nora Franceschini, Claudia Giambartolomei, Paul S de Vries, Chris Finan, Joshua C Bis, Rachael P Huntley, Ruth C Lovering, Salman M Tajuddin, Thomas W Winkler, Misa Graff, Maryam Kavousi, Caroline Dale, Albert V Smith, Edith Hofer, Elisabeth M van Leeuwen, Ilja M Nolte, Lingyi Lu, Markus Scholz, Muralidharan Sargurupremraj, Niina Pitkänen, Oscar Franzén, Peter K Joshi, Raymond Noordam, Riccardo E Marioni, Shih-Jen Hwang, Solomon K Musani, Ulf Schminke, Walter Palmas, Aaron Isaacs, Adolfo Correa, Alan B Zonderman, Albert Hofman, Alexander Teumer, Amanda J Cox, André G Uitterlinden, Andrew Wong, Andries J Smit, Anne B Newman, Annie Britton, Arno Ruusalepp, Bengt Sennblad, Bo Hedblad, Bogdan Pasaniuc, Brenda W Penninx, Carl D Langefeld, Christina L Wassel, Christophe Tzourio, Cristiano Fava, Damiano Baldassarre, Daniel H O'Leary, Daniel Teupser, Diana Kuh, Elena Tremoli, Elmo Mannarino, Enzo Grossi, Eric Boerwinkle, Eric E Schadt, Erik Ingelsson, Fabrizio Veglia, Fernando Rivadeneira, Frank Beutner, Ganesh Chauhan, Gerardo Heiss, Harold Snieder, Harry Campbell, Henry Völzke, Hugh S Markus, Ian J Deary, J Wouter Jukema, Jacqueline de Graaf, Jacqueline Price, Janne Pott, Jemma C Hopewell, Jingjing Liang, Joachim Thiery, Jorgen Engmann, Karl Gertow, Kenneth Rice, Kent D Taylor, Klodian Dhana, Lambertus A L M Kiemeney, Lars Lind, Laura M Raffield, Lenore J Launer, Lesca M Holdt, Marcus Dörr, Martin Dichgans, Matthew Traylor, Matthias Sitzer, Meena Kumari, Mika Kivimaki, Mike A Nalls, Olle Melander, Olli Raitakari, Oscar H Franco, Oscar L Rueda-Ochoa, Panos Roussos, Peter H Whincup, Philippe Amouyel, Philippe Giral, Pramod Anugu, Quenna Wong, Rainer Malik, Rainer Rauramaa, Ralph Burkhardt, Rebecca Hardy, Reinhold Schmidt, Renée de Mutsert, Richard W Morris, Rona J Strawbridge, S Goya Wannamethee, Sara Hägg, Sonia Shah, Stela McLachlan, Stella Trompet, Sudha Seshadri, Sudhir Kurl, Susan R Heckbert, Susan Ring, Tamara B Harris, Terho Lehtimäki, Tessel E Galesloot, Tina Shah, Ulf de Faire, Vincent Plagnol, Wayne D Rosamond, Wendy Post, Xiaofeng Zhu, Xiaoling Zhang, Xiuqing Guo, Yasaman Saba, Abbas Dehghan, Adrie Seldenrijk, Alanna C Morrison, Anders Hamsten, Bruce M Psaty, Cornelia M van Duijn, Deborah A Lawlor, Dennis O Mook-Kanamori, Donald W Bowden, Helena Schmidt, James F Wilson, James G Wilson, Jerome I Rotter, Joanna M Wardlaw, John Deanfield, Julian Halcox, Leo-Pekka Lyytikäinen, Markus Loeffler, Michele K Evans, Stéphanie Debette, Steve E Humphries, Uwe Völker, Vilmundur Gudnason, Aroon D Hingorani, Johan L M Björkegren, Juan P Casas, Christopher J O'Donnell
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4...
December 3, 2018: Nature Communications
https://read.qxmd.com/read/30508554/sleep-duration-and-risk-of-diabetes-observational-and-mendelian-randomization-studies
#20
Jiao Wang, Man Ki Kwok, Shiu Lun Au Yeung, Albert Martin Li, Hugh Simon Lam, June Yue Yan Leung, Lai Ling Hui, Gabriel Matthew Leung, Catherine Mary Schooling
Inadequate sleep could contribute to type 2 diabetes, but observational studies are inconsistent and open to biases, particularly from confounding. We used Mendelian randomization (MR) to obtain an unconfounded estimate of the effect of sleep duration on diabetes, fasting glucose (FG) and hemoglobin A1c (HbA1c), and an observation study to assess differences by sex. Using MR, we assessed the effects of genetically instrumented sleep on diabetes, based on 68 single nucleotide polymorphism (SNP), applied to the DIAbetes Genetics Replication and meta-analysis case (n = 26,676)-control (n = 132,532) study and on FG and HbA1c, based on 55 SNPs, applied to the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) study of FG (n = 122,743) and HbA1c (n = 123,665)...
November 30, 2018: Preventive Medicine
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