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claudin-5 gene

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https://www.readbyqxmd.com/read/29145422/missense-mutation-at-cldn8-associated-with-a-high-plasma-interferon-gamma-inducible-protein-10-level-in-methadone-maintained-patients-with-urine-test-positive-for-morphine
#1
Tung-Hsia Liu, Ren-Hua Chung, Sheng-Chang Wang, Chiu-Ping Fang, Hsiao-Hui Tsou, Chia-Lung Shih, Hsiang-Wei Kuo, Yun Wang, Yu-Li Liu
We previously reported a high plasma chemokine interferon gamma-inducible protein 10 (IP-10) level and prolonged electrocardiography QT-interval in methadone maintenance treatment (MMT) patients with HIV or HCV infection. The purpose of this study was to evaluate the genetic association of high plasma IP-10 level in the MMT patients. The gene-based and pathway-based association analyses were conducted using a genome-wide association study dataset in 344 MMT patients for identifying genes and pathways associated with plasma IP-10 level...
2017: PloS One
https://www.readbyqxmd.com/read/29123511/a-high-grain-diet-dynamically-shifted-the-composition-of-mucosa-associated-microbiota-and-induced-mucosal-injuries-in-the-colon-of-sheep
#2
Yue Wang, Lei Xu, Junhua Liu, Weiyun Zhu, Shengyong Mao
This study investigated the dynamic shifts in mucosa-associated microbiota composition and mucosal morphology in the colon of sheep fed a high grain (HG) diet. A total of 20 male sheep were randomly assigned to four groups (n = 5 for each). The sheep in first group received hay diet. The animals in other 3 groups were fed an HG diet for 7 (HG7), 14 (HG14), or 28 (HG28) days, respectively. Colonic digesta samples were collected to determine the pH and the concentrations of volatile fatty acid (VFA) and lactate...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29107696/the-potential-mechanism-for-hydroxysafflor-yellow-a-attenuating-blood-brain-barrier-dysfunction-via-tight-junction-signaling-pathways-excavated-by-an-integrated-serial-affinity-chromatography-and-shotgun-proteomics-analysis-approach
#3
Yanni Lv, Longsheng Fu
Our previous studies elucidated that hydroxysafflor yellow A (HSYA) exerted anti-inflammatory effects against ischemia stroke by inhibiting TLR4 pathway-mediated signaling transduction. However, only several targets were verified in that limited work. The integrated method of serial affinity chromatography (SAC) and shotgun proteomics analysis (SPA) might be an alternative approach for exploring a potential therapeutic role. SAC was induced to extract specific binding proteins in the brain tissue of 2 h of ischemia stroke mice via HSYA affinity matrices...
October 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29095204/improvement-of-blood-brain-barrier-integrity-in-traumatic-brain-injury-and-hemorrhagic-shock-following-treatment-with-valproic-acid-and-fresh-frozen-plasma
#4
Vahagn C Nikolian, Simone E Dekker, Ted Bambakidis, Gerald A Higgins, Isabel S Dennahy, Patrick E Georgoff, Aaron M Williams, Anuska V Andjelkovic, Hasan B Alam
OBJECTIVE: Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries. Treatment strategies involving plasma-based resuscitation and valproic acid therapy have shown efficacy in this setting. We hypothesize that a component of this beneficial effect is related to blood-brain barrier preservation...
October 31, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/29034530/gene-expression-and-morphological-changes-in-the-intestinal-mucosa-associated-with-increased-permeability-induced-by-short-term-fasting-in-chickens
#5
S Gilani, G S Howarth, G Nattrass, S M Kitessa, R Barekatain, R E A Forder, C D Tran, R J Hughes
Short-term fasting for 4.5 and 9 hr has been demonstrated to increase intestinal permeability (IP) in chickens. This study aimed to investigate the effects of 0, 4.5, 9 and 19.5 hr fasting on intestinal gene expression and villus-crypt architecture of enterocytes in jejunal and ileal samples. On day 38, Ross-308 male birds were fasted according to their group and then euthanised. Two separate intestinal sections (each 2 cm long, jejunum and ileum) were collected. One section was utilised for villus height and crypt depth measurements...
October 16, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28993710/dose-dependent-expression-of-claudin-5-is-a-modifying-factor-in-schizophrenia
#6
C Greene, J Kealy, M M Humphries, Y Gong, J Hou, N Hudson, L M Cassidy, R Martiniano, V Shashi, S R Hooper, G A Grant, P F Kenna, K Norris, C K Callaghan, M dN Islam, S M O'Mara, Z Najda, S G Campbell, J S Pachter, J Thomas, N M Williams, P Humphries, K C Murphy, M Campbell
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells...
October 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28978116/modulation-of-dkk-3-and-claudin-5-as-new-therapeutic-strategy-in-the-treatment-of-meningiomas
#7
Maria Caffo, Emanuela Esposito, Valeria Barresi, Gerardo Caruso, Salvatore M Cardali, Mariagrazia Rinaldi, Raffaella Mallamace, Michela Campolo, Giovanna Casili, Alfredo Conti, Antonino Germanò, Salvatore Cuzzocrea, Letteria Minutoli
Meningiomas are the most common tumors of the central nervous system, where the incidence is around 25% of all primary brain tumors. The optimal treatment is represented by total resection accompanied by the removal of the dura mater and bone when infiltrated by the tumor. The histological grading is the most important prognostic factor in the outcome. However, recurrences do occur in a significant proportion (10-25%) of cases, representing the most relevant clinical complication. Molecular therapies are providing to give different opportunities in the development of new treatments...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28965173/characterization-of-semen-quality-testicular-marker-enzyme-activities-and-gene-expression-changes-in-the-blood-testis-barrier-of-kunming-mice-following-acute-exposure-to-zearalenone
#8
Miao Long, Shuhua Yang, Shuang Dong, Xinliang Chen, Yi Zhang, Jianbin He
A total of 95 8-week-old male Kunming mice were randomly assigned into five groups and exposed to zearalenone (ZEA) at doses of 25, 50, and 75 mg/kg delivered by intra-peritoneal (i.p.) injection for 5 days. The testis and epididymis indices involving sperm quality and morphology, testis enzyme activities, serum concentrations of testosterone and estrogen, and the expression levels of the three gene and protein of N-cadherin, vimentin, and claudin 11 related to the blood testis barrier (BTB) were analyzed...
September 30, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28961379/claudin-5-regulates-blood-brain-barrier-permeability-by-modifying-brain-microvascular-endothelial-cell-proliferation-migration-and-adhesion-to-prevent-lung-cancer-metastasis
#9
Shun-Chang Ma, Qi Li, Jia-Yi Peng, Jian-Long Zhouwen, Jin-Fu Diao, Jian-Xing Niu, Xi Wang, Xiu-Dong Guan, Wang Jia, Wen-Guo Jiang
AIMS: To investigate the roles of Claudin-5 (CLDN5) in regulating the permeability of the blood-brain barrier (BBB) during lung cancer brain metastasis. RESULTS: By silencing and overexpressing the CLDN5 gene in human brain vascular endothelial (hCMEC/D3) cells, we demonstrated the attenuation of cell migration ability and CLDN5's significant positive role in cell proliferation in CLDN5-overexpressing hCMEC/D3 cells and observed the opposite result in the CLDN5 knockdown group...
September 29, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28922365/isothiocyanate-enriched-moringa-seed-extract-alleviates-ulcerative-colitis-symptoms-in-mice
#10
Youjin Kim, Alex G Wu, Asha Jaja-Chimedza, Brittany L Graf, Carrie Waterman, Michael P Verzi, Ilya Raskin
Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA)...
2017: PloS One
https://www.readbyqxmd.com/read/28901429/monocytic-cell-junction-proteins-serve-important-roles-in-atherosclerosis-via-the-endoglin-pathway
#11
Lina Chen, Zhongliang Chen, Menghua Ge, Oushan Tang, Yinhong Cheng, Haoliang Zhou, Yu Shen, Fengming Qin
The formation of atherosclerosis is recognized to be caused by multiple factors including pathogenesis in monocytes during inflammation. The current study provided evidence that monocytic junctions were significantly altered in patients with atherosclerosis, which suggested an association between cell junctions and atherosclerosis. Claudin‑1, occludin‑1 and ZO‑1 were significantly enhanced in atherosclerosis, indicating that the tight junction pathway was activated during the pathogenesis of atherosclerosis...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28889351/multidimensional-phenotyping-of-breast-cancer-cell-lines-to-guide-preclinical-research
#12
Jodi M Saunus, Chanel E Smart, Jamie R Kutasovic, Rebecca L Johnston, Priyakshi Kalita-de Croft, Mariska Miranda, Esdy N Rozali, Ana Cristina Vargas, Lynne E Reid, Eva Lorsy, Sibylle Cocciardi, Tatjana Seidens, Amy E McCart Reed, Andrew J Dalley, Leesa F Wockner, Julie Johnson, Debina Sarkar, Marjan E Askarian-Amiri, Peter T Simpson, Kum Kum Khanna, Georgia Chenevix-Trench, Fares Al-Ejeh, Sunil R Lakhani
PURPOSE: Cell lines are extremely useful tools in breast cancer research. Their key benefits include a high degree of control over experimental variables and reproducibility. However, the advantages must be balanced against the limitations of modelling such a complex disease in vitro. Informed selection of cell line(s) for a given experiment now requires essential knowledge about molecular and phenotypic context in the culture dish. METHODS: We performed multidimensional profiling of 36 widely used breast cancer cell lines that were cultured under standardised conditions...
September 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28888043/sirt1-deacetylates-klf4-to-activate-claudin-5-transcription-in-ovarian-cancer-cells
#13
Xinjian Zhang, Junliang Chen, Lina Sun, Yong Xu
Malignant cancers are distinguished from more benign forms of cancers by enhanced ability to disseminate. A number of factors aid the migration and invasion of malignant cancer cells. Epithelial-to-mesenchymal transition (EMT), which greatly facilitates the dissemination of cancer cells, is characterized by the loss of epithelial markers and the acquisition of mesenchymal markers thereby rendering the cells more migratory and invasive. We have previously shown that the class III lysine deacetylase SIRT1 plays a critical role curbing the metastasis of ovarian cancer cells partly by blocking EMT...
September 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28882639/effects-of-residual-levels-of-tetracycline-on-the-barrier-functions-of-human-intestinal-epithelial-cells
#14
Kuppan Gokulan, Carl E Cerniglia, Charles Thomas, Silvia A Pineiro, Sangeeta Khare
Tetracyclines are frequently used in food-producing animals to treat, control, and prevent microbial diseases. Concerns are raised regarding the effects of residual levels of tetracycline, which may be present in the food supply, for emergence of drug-resistance and transfer of antibiotic-resistance gene in intestinal microbiota. In contrast, no information is available regarding the possible effects of residual tetracycline on the gastrointestinal epithelial layer barrier-disruption. This study investigates the outcome of tetracycline treatment on intestinal epithelial cells integrity...
September 4, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28831972/influence-of-milk-processing-temperature-on-growth-performance-nitrogen-retention-and-hindgut-s-inflammatory-status-and-bacterial-populations-in-a-calf-model
#15
Alex Bach, Anna Aris, Maria Vidal, Francesc Fàbregas, Marta Terré
This research communication describes a study aimed at evaluating the effects of heat treatment of milk on growth performance, N retention, and hindgut's inflammatory status and bacterial populations using young dairy calves as a model. Twenty-one Holstein calves were randomly allocated to one of three treatments: raw milk (RM), pasteurised milk (PAST), or UHT milk (UHT). Calves were submitted to a N balance study, and a biopsy from the distal colon and a faecal sample were obtained from 5 animals per treatment to determine expression of several genes and potential changes in the hindgut's bacterial population...
August 2017: Journal of Dairy Research
https://www.readbyqxmd.com/read/28829370/mir-30a-5p-inhibits-epithelial-to-mesenchymal-transition-and-upregulates-expression-of-tight-junction-protein-claudin-5-in-human-upper-tract-urothelial-carcinoma-cells
#16
Yueh-Hua Chung, Sung-Chou Li, Ying-Hsien Kao, Hao-Lun Luo, Yuan-Tso Cheng, Pey-Ru Lin, Ming-Hong Tai, Po-Hui Chiang
The involvement of microRNAs (miRNAs) in cancer development and their potential as prognostic biomarkers are becoming increasingly known. However, the signature of miRNAs and their regulatory roles in tumorigenesis of upper tract urothelial carcinoma (UTUC) remain to be elucidated. This study aimed to profile the miRNA expression pattern in UTUC tumor tissues and identify candidate miRNAs with prognostic and/or therapeutic functions. METHODS AND RESULTS: We collected 22 UTUC tissue and adjacent normal tissues samples from patients who underwent nephroureterectomy...
August 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28819779/curcuma-wenyujin-y-h-chen-et-c-ling-n-butyl-alcohol-extract-inhibits-ags-cell-helicobacter-pylori-caga-vaca-promoted-invasiveness-by-down-regulating-caudal-type-homeobox-transcription-factor-and-claudin-2-expression
#17
Hai-Feng Jin, Jin-Feng Dai, Li-Na Meng, Bin Lu
OBJECTIVE: To investigate the effects and possible mechanisms of action of Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl alcohol extract (CWNAE) on repression of human gastric cancer (GC) AGS cell invasion induced by co-culturing with Helicobacter pylori (HP). METHODS: AGS cells were cultured with HP of positive or negative cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) expression (CagA+/- or VacA+/-) and divided into 5 group. Group A was cultured without HP as a control, Group B with HPCagA+VacA+, Group C with HPCagA-VacA-, Group D with HPCagA+VacA+ and CWNAE, and Group E with HPCagA-VacA- and CWNAE...
August 17, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28783453/development-of-human-salivary-gland-like-tissue-in-vitro
#18
Marc Burghartz, Simon Lennartz, Matthias Schweinlin, Rudolf Hagen, Norbert Kleinsasser, Stephan Hackenberg, Gudrun Steußloff, Agmal Scherzad, Kathrin Radeloff, Christian Ginzkey, Heike Walles, Marco Metzger
The loss of salivary gland function caused by radiation therapy of the head and neck is a serious condition and it affects a patient's quality of life. The current lack of effective therapies demands new options to be explored. This study tested whether human salivary gland epithelial cells (SGECs) could be successfully cultured on a decellularized porcine gut matrix (SIS-muc) in both mono- and coculture with microvascular endothelial cells (mvECs). By performing immunofluorescence imaging, transmission as well as scanning electron microscopy (SEM), quantitative polymerase chain reaction (qPCR), and an amylase enzyme assay, it was investigated as to what extent the three-dimensional (3D)-cultured cells could maintain their molecular differentiation and the production of working α-amylase (α-AMY) compared with two-dimensional (2D) culture...
August 4, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28715583/tnf%C3%AE-induced-disruption-of-the-blood-retinal-barrier-in-vitro-is-regulated-by-intracellular-3-5-cyclic-adenosine-monophosphate-levels
#19
Anne-Eva van der Wijk, Ilse M C Vogels, Cornelis J F van Noorden, Ingeborg Klaassen, Reinier O Schlingemann
Purpose: Proinflammatory cytokines such as tumor necrosis factor (TNFα) may have a causative role in blood-retinal barrier (BRB) disruption, which is an essential step in the development of diabetic macular edema. The purpose of our study was to determine whether TNFα increases permeability in an in vitro model of the BRB and to explore the mechanisms involved. Methods: Primary bovine retinal endothelial cells (BRECs) were grown on Transwell inserts and cells were stimulated with TNFα or a combination of TNFα, IL1β, and VEGF...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28714976/rare-coding-variants-in-plcg2-abi3-and-trem2-implicate-microglial-mediated-innate-immunity-in-alzheimer-s-disease
#20
Rebecca Sims, Sven J van der Lee, Adam C Naj, Céline Bellenguez, Nandini Badarinarayan, Johanna Jakobsdottir, Brian W Kunkle, Anne Boland, Rachel Raybould, Joshua C Bis, Eden R Martin, Benjamin Grenier-Boley, Stefanie Heilmann-Heimbach, Vincent Chouraki, Amanda B Kuzma, Kristel Sleegers, Maria Vronskaya, Agustin Ruiz, Robert R Graham, Robert Olaso, Per Hoffmann, Megan L Grove, Badri N Vardarajan, Mikko Hiltunen, Markus M Nöthen, Charles C White, Kara L Hamilton-Nelson, Jacques Epelbaum, Wolfgang Maier, Seung-Hoan Choi, Gary W Beecham, Cécile Dulary, Stefan Herms, Albert V Smith, Cory C Funk, Céline Derbois, Andreas J Forstner, Shahzad Ahmad, Hongdong Li, Delphine Bacq, Denise Harold, Claudia L Satizabal, Otto Valladares, Alessio Squassina, Rhodri Thomas, Jennifer A Brody, Liming Qu, Pascual Sánchez-Juan, Taniesha Morgan, Frank J Wolters, Yi Zhao, Florentino Sanchez Garcia, Nicola Denning, Myriam Fornage, John Malamon, Maria Candida Deniz Naranjo, Elisa Majounie, Thomas H Mosley, Beth Dombroski, David Wallon, Michelle K Lupton, Josée Dupuis, Patrice Whitehead, Laura Fratiglioni, Christopher Medway, Xueqiu Jian, Shubhabrata Mukherjee, Lina Keller, Kristelle Brown, Honghuang Lin, Laura B Cantwell, Francesco Panza, Bernadette McGuinness, Sonia Moreno-Grau, Jeremy D Burgess, Vincenzo Solfrizzi, Petra Proitsi, Hieab H Adams, Mariet Allen, Davide Seripa, Pau Pastor, L Adrienne Cupples, Nathan D Price, Didier Hannequin, Ana Frank-García, Daniel Levy, Paramita Chakrabarty, Paolo Caffarra, Ina Giegling, Alexa S Beiser, Vilmantas Giedraitis, Harald Hampel, Melissa E Garcia, Xue Wang, Lars Lannfelt, Patrizia Mecocci, Gudny Eiriksdottir, Paul K Crane, Florence Pasquier, Virginia Boccardi, Isabel Henández, Robert C Barber, Martin Scherer, Lluis Tarraga, Perrie M Adams, Markus Leber, Yuning Chen, Marilyn S Albert, Steffi Riedel-Heller, Valur Emilsson, Duane Beekly, Anne Braae, Reinhold Schmidt, Deborah Blacker, Carlo Masullo, Helena Schmidt, Rachelle S Doody, Gianfranco Spalletta, W T Longstreth Jr, Thomas J Fairchild, Paola Bossù, Oscar L Lopez, Matthew P Frosch, Eleonora Sacchinelli, Bernardino Ghetti, Qiong Yang, Ryan M Huebinger, Frank Jessen, Shuo Li, M Ilyas Kamboh, John Morris, Oscar Sotolongo-Grau, Mindy J Katz, Chris Corcoran, Melanie Dunstan, Amy Braddel, Charlene Thomas, Alun Meggy, Rachel Marshall, Amy Gerrish, Jade Chapman, Miquel Aguilar, Sarah Taylor, Matt Hill, Mònica Díez Fairén, Angela Hodges, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Makrina Daniilidou, James Uphill, Yogen Patel, Joseph T Hughes, Jenny Lord, James Turton, Annette M Hartmann, Roberta Cecchetti, Chiara Fenoglio, Maria Serpente, Marina Arcaro, Carlo Caltagirone, Maria Donata Orfei, Antonio Ciaramella, Sabrina Pichler, Manuel Mayhaus, Wei Gu, Alberto Lleó, Juan Fortea, Rafael Blesa, Imelda S Barber, Keeley Brookes, Chiara Cupidi, Raffaele Giovanni Maletta, David Carrell, Sandro Sorbi, Susanne Moebus, Maria Urbano, Alberto Pilotto, Johannes Kornhuber, Paolo Bosco, Stephen Todd, David Craig, Janet Johnston, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Nick C Fox, John Hardy, Roger L Albin, Liana G Apostolova, Steven E Arnold, Sanjay Asthana, Craig S Atwood, Clinton T Baldwin, Lisa L Barnes, Sandra Barral, Thomas G Beach, James T Becker, Eileen H Bigio, Thomas D Bird, Bradley F Boeve, James D Bowen, Adam Boxer, James R Burke, Jeffrey M Burns, Joseph D Buxbaum, Nigel J Cairns, Chuanhai Cao, Chris S Carlson, Cynthia M Carlsson, Regina M Carney, Minerva M Carrasquillo, Steven L Carroll, Carolina Ceballos Diaz, Helena C Chui, David G Clark, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Malcolm Dick, Ranjan Duara, Denis A Evans, Kelley M Faber, Kenneth B Fallon, David W Fardo, Martin R Farlow, Steven Ferris, Tatiana M Foroud, Douglas R Galasko, Marla Gearing, Daniel H Geschwind, John R Gilbert, Neill R Graff-Radford, Robert C Green, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Lawrence S Honig, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Gail P Jarvik, Erin Abner, Lee-Way Jin, Gyungah Jun, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Neil W Kowall, Joel H Kramer, Frank M LaFerla, James J Lah, James B Leverenz, Allan I Levey, Ge Li, Andrew P Lieberman, Kathryn L Lunetta, Constantine G Lyketsos, Daniel C Marson, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, John C Morris, Jill R Murrell, Amanda J Myers, Sid O'Bryant, John M Olichney, Vernon S Pankratz, Joseph E Parisi, Henry L Paulson, William Perry, Elaine Peskind, Aimee Pierce, Wayne W Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Barry Reisberg, Christiane Reitz, John M Ringman, Erik D Roberson, Ekaterina Rogaeva, Howard J Rosen, Roger N Rosenberg, Mark A Sager, Andrew J Saykin, Julie A Schneider, Lon S Schneider, William W Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Russell H Swerdlow, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Vivianna M Van Deerlin, Linda J Van Eldik, Harry V Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Kirk C Wilhelmsen, Jennifer Williamson, Thomas S Wingo, Randall L Woltjer, Clinton B Wright, Chang-En Yu, Lei Yu, Fabienne Garzia, Feroze Golamaully, Gislain Septier, Sebastien Engelborghs, Rik Vandenberghe, Peter P De Deyn, Carmen Muñoz Fernadez, Yoland Aladro Benito, Hakan Thonberg, Charlotte Forsell, Lena Lilius, Anne Kinhult-Stählbom, Lena Kilander, RoseMarie Brundin, Letizia Concari, Seppo Helisalmi, Anne Maria Koivisto, Annakaisa Haapasalo, Vincent Dermecourt, Nathalie Fievet, Olivier Hanon, Carole Dufouil, Alexis Brice, Karen Ritchie, Bruno Dubois, Jayanadra J Himali, C Dirk Keene, JoAnn Tschanz, Annette L Fitzpatrick, Walter A Kukull, Maria Norton, Thor Aspelund, Eric B Larson, Ron Munger, Jerome I Rotter, Richard B Lipton, María J Bullido, Albert Hofman, Thomas J Montine, Eliecer Coto, Eric Boerwinkle, Ronald C Petersen, Victoria Alvarez, Fernando Rivadeneira, Eric M Reiman, Maura Gallo, Christopher J O'Donnell, Joan S Reisch, Amalia Cecilia Bruni, Donald R Royall, Martin Dichgans, Mary Sano, Daniela Galimberti, Peter St George-Hyslop, Elio Scarpini, Debby W Tsuang, Michelangelo Mancuso, Ubaldo Bonuccelli, Ashley R Winslow, Antonio Daniele, Chuang-Kuo Wu, Oliver Peters, Benedetta Nacmias, Matthias Riemenschneider, Reinhard Heun, Carol Brayne, David C Rubinsztein, Jose Bras, Rita Guerreiro, Ammar Al-Chalabi, Christopher E Shaw, John Collinge, David Mann, Magda Tsolaki, Jordi Clarimón, Rebecca Sussams, Simon Lovestone, Michael C O'Donovan, Michael J Owen, Timothy W Behrens, Simon Mead, Alison M Goate, Andre G Uitterlinden, Clive Holmes, Carlos Cruchaga, Martin Ingelsson, David A Bennett, John Powell, Todd E Golde, Caroline Graff, Philip L De Jager, Kevin Morgan, Nilufer Ertekin-Taner, Onofre Combarros, Bruce M Psaty, Peter Passmore, Steven G Younkin, Claudine Berr, Vilmundur Gudnason, Dan Rujescu, Dennis W Dickson, Jean-François Dartigues, Anita L DeStefano, Sara Ortega-Cubero, Hakon Hakonarson, Dominique Campion, Merce Boada, John Keoni Kauwe, Lindsay A Farrer, Christine Van Broeckhoven, M Arfan Ikram, Lesley Jones, Jonathan L Haines, Christophe Tzourio, Lenore J Launer, Valentina Escott-Price, Richard Mayeux, Jean-François Deleuze, Najaf Amin, Peter A Holmans, Margaret A Pericak-Vance, Philippe Amouyel, Cornelia M van Duijn, Alfredo Ramirez, Li-San Wang, Jean-Charles Lambert, Sudha Seshadri, Julie Williams, Gerard D Schellenberg
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10(-8)) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p...
September 2017: Nature Genetics
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