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Book ; Online ; Thesis: Next-generation sequencing of centenarians to identify genetic variants predisposing to human longevity

2018

Author's details	Nandini Badarinarayan
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	English
Publisher	Universitätsbibliothek Kiel
Publishing place	Kiel
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Polymorphisms in the superoxidase dismutase genes reveal no association with human longevity in Germans: a case-control association study.

Gentschew, Liljana / Flachsbart, Friederike / Kleindorp, Rabea / Badarinarayan, Nandini / Schreiber, Stefan / Nebel, Almut

Biogerontology

2013 Volume 14, Issue 6, Page(s) 719–727

Abstract: The role of superoxide dismutases (SODs) in aging and oxidative stress regulation has been widely studied and there is growing evidence that imbalances in these processes influence lifespan in several species. In humans, genetic polymorphisms in SOD ... ...

Abstract	The role of superoxide dismutases (SODs) in aging and oxidative stress regulation has been widely studied and there is growing evidence that imbalances in these processes influence lifespan in several species. In humans, genetic polymorphisms in SOD genes may play an important role in the development of age-related diseases and genetic variation in SOD2 is thought to be associated with longevity. These observations prompted us to perform a case-control association study using a comprehensive haplotype tagging approach for the three SOD genes (SOD1, SOD2, SOD3) by testing a total of 19 SNPs in our extensive collection of 1,612 long-lived individuals (centenarians and nonagenarians) and 1,104 younger controls. Furthermore, we intended to replicate the previous association of the SOD2 SNP rs4880 with longevity observed in a Danish cohort. In our study, no association was detected between the tested SNPs and the longevity phenotype, neither in the entire long-lived sample set nor in the centenarian subgroup analysis. Our results suggest that there is no considerable influence of sequence variation in the SOD genes on human longevity in Germans.
MeSH term(s)	Aged, 80 and over ; Case-Control Studies ; Female ; Gene Frequency ; Germany ; Haplotypes ; Humans ; Longevity/genetics ; Male ; Phenotype ; Polymorphism, Single Nucleotide ; Superoxide Dismutase/genetics ; Superoxide Dismutase-1
Chemical Substances	SOD1 protein, human ; SOD3 protein, human (EC 1.15.1.1) ; Superoxide Dismutase (EC 1.15.1.1) ; Superoxide Dismutase-1 (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1)
Language	English
Publishing date	2013-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2047160-9
ISSN	1573-6768 ; 1389-5729
ISSN (online)	1573-6768
ISSN	1389-5729
DOI	10.1007/s10522-013-9470-3
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Article ; Online: Publisher Correction: Identification and characterization of two functional variants in the human longevity gene FOXO3.

Flachsbart, Friederike / Dose, Janina / Gentschew, Liljana / Geismann, Claudia / Caliebe, Amke / Knecht, Carolin / Nygaard, Marianne / Badarinarayan, Nandini / ElSharawy, Abdou / May, Sandra / Luzius, Anne / Torres, Guillermo G / Jentzsch, Marlene / Forster, Michael / Häsler, Robert / Pallauf, Kathrin / Lieb, Wolfgang / Derbois, Céline / Galan, Pilar /

Drichel, Dmitriy / Arlt, Alexander / Till, Andreas / Krause-Kyora, Ben / Rimbach, Gerald / Blanché, Hélène / Deleuze, Jean-François / Christiansen, Lene / Christensen, Kaare / Nothnagel, Michael / Rosenstiel, Philip / Schreiber, Stefan / Franke, Andre / Sebens, Susanne / Nebel, Almut

Nature communications

2018 Volume 9, Issue 1, Page(s) 320

Abstract: The original version of this Article contained an error in the spelling of the author Robert Häsler, which was incorrectly given as Robert Häesler. This has now been corrected in both the PDF and HTML versions of the Article. ...

Abstract	The original version of this Article contained an error in the spelling of the author Robert Häsler, which was incorrectly given as Robert Häesler. This has now been corrected in both the PDF and HTML versions of the Article.
Language	English
Publishing date	2018-01-17
Publishing country	England
Document type	Journal Article ; Published Erratum
ISSN	2041-1723
ISSN (online)	2041-1723
DOI	10.1038/s41467-018-02842-8
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Article ; Online: Identification and characterization of two functional variants in the human longevity gene FOXO3.

Nature communications

2017 Volume 8, Issue 1, Page(s) 2063

Abstract: FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three ...

Abstract	FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays, the longevity alleles of both variants show considerable enhancer activities that are reversed by IGF-1 treatment. An eQTL database search reveals that the alleles are also associated with higher FOXO3 mRNA expression in various human tissues, which is in line with observations in long-lived model organisms. In summary, we present experimental evidence for a functional link between common intronic variants in FOXO3 and human longevity.
MeSH term(s)	Age Factors ; Aged ; Aged, 80 and over ; Alleles ; CCCTC-Binding Factor/genetics ; CCCTC-Binding Factor/metabolism ; Computer Simulation ; European Continental Ancestry Group/genetics ; Female ; Forkhead Box Protein O3/genetics ; Forkhead Box Protein O3/physiology ; Haplotypes/genetics ; Humans ; Insulin-Like Growth Factor I/metabolism ; Introns/genetics ; Longevity/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; RNA, Messenger/metabolism ; Serum Response Factor/genetics ; Serum Response Factor/metabolism
Chemical Substances	CCCTC-Binding Factor ; CTCF protein, human ; FOXO3 protein, human ; Forkhead Box Protein O3 ; IGF1 protein, human ; RNA, Messenger ; SRF protein, human ; Serum Response Factor ; Insulin-Like Growth Factor I (67763-96-6)
Language	English
Publishing date	2017-12-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2041-1723
ISSN (online)	2041-1723
DOI	10.1038/s41467-017-02183-y
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Article ; Online: Common polygenic variation enhances risk prediction for Alzheimer's disease.

Escott-Price, Valentina / Sims, Rebecca / Bannister, Christian / Harold, Denise / Vronskaya, Maria / Majounie, Elisa / Badarinarayan, Nandini / Morgan, Kevin / Passmore, Peter / Holmes, Clive / Powell, John / Brayne, Carol / Gill, Michael / Mead, Simon / Goate, Alison / Cruchaga, Carlos / Lambert, Jean-Charles / van Duijn, Cornelia / Maier, Wolfgang /

Ramirez, Alfredo / Holmans, Peter / Jones, Lesley / Hardy, John / Seshadri, Sudha / Schellenberg, Gerard D / Amouyel, Philippe / Williams, Julie

Brain : a journal of neurology

2015 Volume 138, Issue Pt 12, Page(s) 3673–3684

Abstract: The identification of subjects at high risk for Alzheimer's disease is important for prognosis and early intervention. We investigated the polygenic architecture of Alzheimer's disease and the accuracy of Alzheimer's disease prediction models, including ... ...

Abstract	The identification of subjects at high risk for Alzheimer's disease is important for prognosis and early intervention. We investigated the polygenic architecture of Alzheimer's disease and the accuracy of Alzheimer's disease prediction models, including and excluding the polygenic component in the model. This study used genotype data from the powerful dataset comprising 17 008 cases and 37 154 controls obtained from the International Genomics of Alzheimer's Project (IGAP). Polygenic score analysis tested whether the alleles identified to associate with disease in one sample set were significantly enriched in the cases relative to the controls in an independent sample. The disease prediction accuracy was investigated in a subset of the IGAP data, a sample of 3049 cases and 1554 controls (for whom APOE genotype data were available) by means of sensitivity, specificity, area under the receiver operating characteristic curve (AUC) and positive and negative predictive values. We observed significant evidence for a polygenic component enriched in Alzheimer's disease (P = 4.9 × 10(-26)). This enrichment remained significant after APOE and other genome-wide associated regions were excluded (P = 3.4 × 10(-19)). The best prediction accuracy AUC = 78.2% (95% confidence interval 77-80%) was achieved by a logistic regression model with APOE, the polygenic score, sex and age as predictors. In conclusion, Alzheimer's disease has a significant polygenic component, which has predictive utility for Alzheimer's disease risk and could be a valuable research tool complementing experimental designs, including preventative clinical trials, stem cell selection and high/low risk clinical studies. In modelling a range of sample disease prevalences, we found that polygenic scores almost doubles case prediction from chance with increased prediction at polygenic extremes.
MeSH term(s)	Alleles ; Alzheimer Disease/genetics ; Apolipoproteins E/genetics ; Case-Control Studies ; Genetic Predisposition to Disease/genetics ; Genetic Testing ; Genetic Variation/genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Logistic Models ; Multifactorial Inheritance/genetics ; ROC Curve ; Risk
Chemical Substances	Apolipoproteins E
Language	English
Publishing date	2015-10-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awv268
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Article ; Online: Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.

Fischer, Ute / Forster, Michael / Rinaldi, Anna / Risch, Thomas / Sungalee, Stéphanie / Warnatz, Hans-Jörg / Bornhauser, Beat / Gombert, Michael / Kratsch, Christina / Stütz, Adrian M / Sultan, Marc / Tchinda, Joelle / Worth, Catherine L / Amstislavskiy, Vyacheslav / Badarinarayan, Nandini / Baruchel, André / Bartram, Thies / Basso, Giuseppe / Canpolat, Cengiz /

Cario, Gunnar / Cavé, Hélène / Dakaj, Dardane / Delorenzi, Mauro / Dobay, Maria Pamela / Eckert, Cornelia / Ellinghaus, Eva / Eugster, Sabrina / Frismantas, Viktoras / Ginzel, Sebastian / Haas, Oskar A / Heidenreich, Olaf / Hemmrich-Stanisak, Georg / Hezaveh, Kebria / Höll, Jessica I / Hornhardt, Sabine / Husemann, Peter / Kachroo, Priyadarshini / Kratz, Christian P / Te Kronnie, Geertruy / Marovca, Blerim / Niggli, Felix / McHardy, Alice C / Moorman, Anthony V / Panzer-Grümayer, Renate / Petersen, Britt S / Raeder, Benjamin / Ralser, Meryem / Rosenstiel, Philip / Schäfer, Daniel / Schrappe, Martin / Schreiber, Stefan / Schütte, Moritz / Stade, Björn / Thiele, Ralf / von der Weid, Nicolas / Vora, Ajay / Zaliova, Marketa / Zhang, Langhui / Zichner, Thomas / Zimmermann, Martin / Lehrach, Hans / Borkhardt, Arndt / Bourquin, Jean-Pierre / Franke, Andre / Korbel, Jan O / Stanulla, Martin / Yaspo, Marie-Laure

Nature genetics

2015 Volume 47, Issue 9, Page(s) 1020–1029

Abstract: TCF3-HLF-positive acute lymphoblastic leukemia (ALL) is currently incurable. Using an integrated approach, we uncovered distinct mutation, gene expression and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. We ...

Abstract	TCF3-HLF-positive acute lymphoblastic leukemia (ALL) is currently incurable. Using an integrated approach, we uncovered distinct mutation, gene expression and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. We identified recurrent intragenic deletions of PAX5 or VPREB1 in constellation with the fusion of TCF3 and HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin toward a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Coculture Techniques ; Cohort Studies ; DNA Mutational Analysis ; Drug Resistance, Neoplasm ; Female ; Gene Expression ; Genetic Association Studies ; Genomics ; Humans ; Immunoglobulin Light Chains, Surrogate/genetics ; Inhibitory Concentration 50 ; Kaplan-Meier Estimate ; Male ; Mice, Inbred NOD ; Mice, SCID ; Mutation ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; PAX5 Transcription Factor/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality ; Sequence Deletion ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Immunoglobulin Light Chains, Surrogate ; Oncogene Proteins, Fusion ; PAX5 Transcription Factor ; PAX5 protein, human ; TCF3-HLF fusion protein, human ; VPREB1 protein, human
Language	English
Publishing date	2015-07-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/ng.3362
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Article ; Online: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Kunkle, Brian W / Grenier-Boley, Benjamin / Sims, Rebecca / Bis, Joshua C / Damotte, Vincent / Naj, Adam C / Boland, Anne / Vronskaya, Maria / van der Lee, Sven J / Amlie-Wolf, Alexandre / Bellenguez, Céline / Frizatti, Aura / Chouraki, Vincent / Martin, Eden R / Sleegers, Kristel / Badarinarayan, Nandini / Jakobsdottir, Johanna / Hamilton-Nelson, Kara L / Moreno-Grau, Sonia /

Olaso, Robert / Raybould, Rachel / Chen, Yuning / Kuzma, Amanda B / Hiltunen, Mikko / Morgan, Taniesha / Ahmad, Shahzad / Vardarajan, Badri N / Epelbaum, Jacques / Hoffmann, Per / Boada, Merce / Beecham, Gary W / Garnier, Jean-Guillaume / Harold, Denise / Fitzpatrick, Annette L / Valladares, Otto / Moutet, Marie-Laure / Gerrish, Amy / Smith, Albert V / Qu, Liming / Bacq, Delphine / Denning, Nicola / Jian, Xueqiu / Zhao, Yi / Del Zompo, Maria / Fox, Nick C / Choi, Seung-Hoan / Mateo, Ignacio / Hughes, Joseph T / Adams, Hieab H / Malamon, John / Sanchez-Garcia, Florentino / Patel, Yogen / Brody, Jennifer A / Dombroski, Beth A / Naranjo, Maria Candida Deniz / Daniilidou, Makrina / Eiriksdottir, Gudny / Mukherjee, Shubhabrata / Wallon, David / Uphill, James / Aspelund, Thor / Cantwell, Laura B / Garzia, Fabienne / Galimberti, Daniela / Hofer, Edith / Butkiewicz, Mariusz / Fin, Bertrand / Scarpini, Elio / Sarnowski, Chloe / Bush, Will S / Meslage, Stéphane / Kornhuber, Johannes / White, Charles C / Song, Yuenjoo / Barber, Robert C / Engelborghs, Sebastiaan / Sordon, Sabrina / Voijnovic, Dina / Adams, Perrie M / Vandenberghe, Rik / Mayhaus, Manuel / Cupples, L Adrienne / Albert, Marilyn S / De Deyn, Peter P / Gu, Wei / Himali, Jayanadra J / Beekly, Duane / Squassina, Alessio / Hartmann, Annette M / Orellana, Adelina / Blacker, Deborah / Rodriguez-Rodriguez, Eloy / Lovestone, Simon / Garcia, Melissa E / Doody, Rachelle S / Munoz-Fernadez, Carmen / Sussams, Rebecca / Lin, Honghuang / Fairchild, Thomas J / Benito, Yolanda A / Holmes, Clive / Karamujić-Čomić, Hata / Frosch, Matthew P / Thonberg, Hakan / Maier, Wolfgang / Roshchupkin, Gennady / Ghetti, Bernardino / Giedraitis, Vilmantas / Kawalia, Amit / Li, Shuo / Huebinger, Ryan M / Kilander, Lena / Moebus, Susanne / Hernández, Isabel / Kamboh, M Ilyas / Brundin, RoseMarie / Turton, James / Yang, Qiong / Katz, Mindy J / Concari, Letizia / Lord, Jenny / Beiser, Alexa S / Keene, C Dirk / Helisalmi, Seppo / Kloszewska, Iwona / Kukull, Walter A / Koivisto, Anne Maria / Lynch, Aoibhinn / Tarraga, Lluís / Larson, Eric B / Haapasalo, Annakaisa / Lawlor, Brian / Mosley, Thomas H / Lipton, Richard B / Solfrizzi, Vincenzo / Gill, Michael / Longstreth, W T / Montine, Thomas J / Frisardi, Vincenza / Diez-Fairen, Monica / Rivadeneira, Fernando / Petersen, Ronald C / Deramecourt, Vincent / Alvarez, Ignacio / Salani, Francesca / Ciaramella, Antonio / Boerwinkle, Eric / Reiman, Eric M / Fievet, Nathalie / Rotter, Jerome I / Reisch, Joan S / Hanon, Olivier / Cupidi, Chiara / Andre Uitterlinden, A G / Royall, Donald R / Dufouil, Carole / Maletta, Raffaele Giovanni / de Rojas, Itziar / Sano, Mary / Brice, Alexis / Cecchetti, Roberta / George-Hyslop, Peter St / Ritchie, Karen / Tsolaki, Magda / Tsuang, Debby W / Dubois, Bruno / Craig, David / Wu, Chuang-Kuo / Soininen, Hilkka / Avramidou, Despoina / Albin, Roger L / Fratiglioni, Laura / Germanou, Antonia / Apostolova, Liana G / Keller, Lina / Koutroumani, Maria / Arnold, Steven E / Panza, Francesco / Gkatzima, Olymbia / Asthana, Sanjay / Hannequin, Didier / Whitehead, Patrice / Atwood, Craig S / Caffarra, Paolo / Hampel, Harald / Quintela, Inés / Carracedo, Ángel / Lannfelt, Lars / Rubinsztein, David C / Barnes, Lisa L / Pasquier, Florence / Frölich, Lutz / Barral, Sandra / McGuinness, Bernadette / Beach, Thomas G / Johnston, Janet A / Becker, James T / Passmore, Peter / Bigio, Eileen H / Schott, Jonathan M / Bird, Thomas D / Warren, Jason D / Boeve, Bradley F / Lupton, Michelle K / Bowen, James D / Proitsi, Petra / Boxer, Adam / Powell, John F / Burke, James R / Kauwe, John S K / Burns, Jeffrey M / Mancuso, Michelangelo / Buxbaum, Joseph D / Bonuccelli, Ubaldo / Cairns, Nigel J / McQuillin, Andrew / Cao, Chuanhai / Livingston, Gill / Carlson, Chris S / Bass, Nicholas J / Carlsson, Cynthia M / Hardy, John / Carney, Regina M / Bras, Jose / Carrasquillo, Minerva M / Guerreiro, Rita / Allen, Mariet / Chui, Helena C / Fisher, Elizabeth / Masullo, Carlo / Crocco, Elizabeth A / DeCarli, Charles / Bisceglio, Gina / Dick, Malcolm / Ma, Li / Duara, Ranjan / Graff-Radford, Neill R / Evans, Denis A / Hodges, Angela / Faber, Kelley M / Scherer, Martin / Fallon, Kenneth B / Riemenschneider, Matthias / Fardo, David W / Heun, Reinhard / Farlow, Martin R / Kölsch, Heike / Ferris, Steven / Leber, Markus / Foroud, Tatiana M / Heuser, Isabella / Galasko, Douglas R / Giegling, Ina / Gearing, Marla / Hüll, Michael / Geschwind, Daniel H / Gilbert, John R / Morris, John / Green, Robert C / Mayo, Kevin / Growdon, John H / Feulner, Thomas / Hamilton, Ronald L / Harrell, Lindy E / Drichel, Dmitriy / Honig, Lawrence S / Cushion, Thomas D / Huentelman, Matthew J / Hollingworth, Paul / Hulette, Christine M / Hyman, Bradley T / Marshall, Rachel / Jarvik, Gail P / Meggy, Alun / Abner, Erin / Menzies, Georgina E / Jin, Lee-Way / Leonenko, Ganna / Real, Luis M / Jun, Gyungah R / Baldwin, Clinton T / Grozeva, Detelina / Karydas, Anna / Russo, Giancarlo / Kaye, Jeffrey A / Kim, Ronald / Jessen, Frank / Kowall, Neil W / Vellas, Bruno / Kramer, Joel H / Vardy, Emma / LaFerla, Frank M / Jöckel, Karl-Heinz / Lah, James J / Dichgans, Martin / Leverenz, James B / Mann, David / Levey, Allan I / Pickering-Brown, Stuart / Lieberman, Andrew P / Klopp, Norman / Lunetta, Kathryn L / Wichmann, H-Erich / Lyketsos, Constantine G / Morgan, Kevin / Marson, Daniel C / Brown, Kristelle / Martiniuk, Frank / Medway, Christopher / Mash, Deborah C / Nöthen, Markus M / Masliah, Eliezer / Hooper, Nigel M / McCormick, Wayne C / Daniele, Antonio / McCurry, Susan M / Bayer, Anthony / McDavid, Andrew N / Gallacher, John / McKee, Ann C / van den Bussche, Hendrik / Mesulam, Marsel / Brayne, Carol / Miller, Bruce L / Riedel-Heller, Steffi / Miller, Carol A / Miller, Joshua W / Al-Chalabi, Ammar / Morris, John C / Shaw, Christopher E / Myers, Amanda J / Wiltfang, Jens / O'Bryant, Sid / Olichney, John M / Alvarez, Victoria / Parisi, Joseph E / Singleton, Andrew B / Paulson, Henry L / Collinge, John / Perry, William R / Mead, Simon / Peskind, Elaine / Cribbs, David H / Rossor, Martin / Pierce, Aimee / Ryan, Natalie S / Poon, Wayne W / Nacmias, Benedetta / Potter, Huntington / Sorbi, Sandro / Quinn, Joseph F / Sacchinelli, Eleonora / Raj, Ashok / Spalletta, Gianfranco / Raskind, Murray / Caltagirone, Carlo / Bossù, Paola / Orfei, Maria Donata / Reisberg, Barry / Clarke, Robert / Reitz, Christiane / Smith, A David / Ringman, John M / Warden, Donald / Roberson, Erik D / Wilcock, Gordon / Rogaeva, Ekaterina / Bruni, Amalia Cecilia / Rosen, Howard J / Gallo, Maura / Rosenberg, Roger N / Ben-Shlomo, Yoav / Sager, Mark A / Mecocci, Patrizia / Saykin, Andrew J / Pastor, Pau / Cuccaro, Michael L / Vance, Jeffery M / Schneider, Julie A / Schneider, Lori S / Slifer, Susan / Seeley, William W / Smith, Amanda G / Sonnen, Joshua A / Spina, Salvatore / Stern, Robert A / Swerdlow, Russell H / Tang, Mitchell / Tanzi, Rudolph E / Trojanowski, John Q / Troncoso, Juan C / Van Deerlin, Vivianna M / Van Eldik, Linda J / Vinters, Harry V / Vonsattel, Jean Paul / Weintraub, Sandra / Welsh-Bohmer, Kathleen A / Wilhelmsen, Kirk C / Williamson, Jennifer / Wingo, Thomas S / Woltjer, Randall L / Wright, Clinton B / Yu, Chang-En / Yu, Lei / Saba, Yasaman / Pilotto, Alberto / Bullido, Maria J / Peters, Oliver / Crane, Paul K / Bennett, David / Bosco, Paola / Coto, Eliecer / Boccardi, Virginia / De Jager, Phil L / Lleo, Alberto / Warner, Nick / Lopez, Oscar L / Ingelsson, Martin / Deloukas, Panagiotis / Cruchaga, Carlos / Graff, Caroline / Gwilliam, Rhian / Fornage, Myriam / Goate, Alison M / Sanchez-Juan, Pascual / Kehoe, Patrick G / Amin, Najaf / Ertekin-Taner, Nilifur / Berr, Claudine / Debette, Stéphanie / Love, Seth / Launer, Lenore J / Younkin, Steven G / Dartigues, Jean-Francois / Corcoran, Chris / Ikram, M Arfan / Dickson, Dennis W / Nicolas, Gael / Campion, Dominique / Tschanz, JoAnn / Schmidt, Helena / Hakonarson, Hakon / Clarimon, Jordi / Munger, Ron / Schmidt, Reinhold / Farrer, Lindsay A / Van Broeckhoven, Christine / C O'Donovan, Michael / DeStefano, Anita L / Jones, Lesley / Haines, Jonathan L / Deleuze, Jean-Francois / Owen, Michael J / Gudnason, Vilmundur / Mayeux, Richard / Escott-Price, Valentina / Psaty, Bruce M / Ramirez, Alfredo / Wang, Li-San / Ruiz, Agustin / van Duijn, Cornelia M / Holmans, Peter A / Seshadri, Sudha / Williams, Julie / Amouyel, Phillippe / Schellenberg, Gerard D / Lambert, Jean-Charles / Pericak-Vance, Margaret A

Nature genetics

2019 Volume 51, Issue 3, Page(s) 414–430

Abstract: Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We ... ...

Abstract	Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10
MeSH term(s)	Aged ; Alzheimer Disease/genetics ; Amyloid beta-Peptides/genetics ; Case-Control Studies ; Female ; Genetic Loci/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Testing/methods ; Genome-Wide Association Study/methods ; Haplotypes/genetics ; Humans ; Immunity/genetics ; Lipid Metabolism/genetics ; Lipids/genetics ; Male ; tau Proteins/genetics
Chemical Substances	Amyloid beta-Peptides ; Lipids ; tau Proteins
Language	English
Publishing date	2019-02-28
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-019-0358-2
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Article ; Online: Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Olaso, Robert / Raybould, Rachel / Chen, Yuning / Kuzma, Amanda B / Hiltunen, Mikko / Morgan, Taniesha / Ahmad, Shahzad / Vardarajan, Badri N / Epelbaum, Jacques / Hoffmann, Per / Boada, Merce / Beecham, Gary W / Garnier, Jean-Guillaume / Harold, Denise / Fitzpatrick, Annette L / Valladares, Otto / Moutet, Marie-Laure / Gerrish, Amy / Smith, Albert V / Qu, Liming / Bacq, Delphine / Denning, Nicola / Jian, Xueqiu / Zhao, Yi / Del Zompo, Maria / Fox, Nick C / Choi, Seung-Hoan / Mateo, Ignacio / Hughes, Joseph T / Adams, Hieab H / Malamon, John / Sanchez-Garcia, Florentino / Patel, Yogen / Brody, Jennifer A / Dombroski, Beth A / Naranjo, Maria Candida Deniz / Daniilidou, Makrina / Eiriksdottir, Gudny / Mukherjee, Shubhabrata / Wallon, David / Uphill, James / Aspelund, Thor / Cantwell, Laura B / Garzia, Fabienne / Galimberti, Daniela / Hofer, Edith / Butkiewicz, Mariusz / Fin, Bertrand / Scarpini, Elio / Sarnowski, Chloe / Bush, Will S / Meslage, Stéphane / Kornhuber, Johannes / White, Charles C / Song, Yuenjoo / Barber, Robert C / Engelborghs, Sebastiaan / Sordon, Sabrina / Voijnovic, Dina / Adams, Perrie M / Vandenberghe, Rik / Mayhaus, Manuel / Cupples, L Adrienne / Albert, Marilyn S / De Deyn, Peter P / Gu, Wei / Himali, Jayanadra J / Beekly, Duane / Squassina, Alessio / Hartmann, Annette M / Orellana, Adelina / Blacker, Deborah / Rodriguez-Rodriguez, Eloy / Lovestone, Simon / Garcia, Melissa E / Doody, Rachelle S / Munoz-Fernadez, Carmen / Sussams, Rebecca / Lin, Honghuang / Fairchild, Thomas J / Benito, Yolanda A / Holmes, Clive / Karamujić-Čomić, Hata / Frosch, Matthew P / Thonberg, Hakan / Maier, Wolfgang / Roshchupkin, Gennady / Ghetti, Bernardino / Giedraitis, Vilmantas / Kawalia, Amit / Li, Shuo / Huebinger, Ryan M / Kilander, Lena / Moebus, Susanne / Hernández, Isabel / Kamboh, M Ilyas / Brundin, RoseMarie / Turton, James / Yang, Qiong / Katz, Mindy J / Concari, Letizia / Lord, Jenny / Beiser, Alexa S / Keene, C Dirk / Helisalmi, Seppo / Kloszewska, Iwona / Kukull, Walter A / Koivisto, Anne Maria / Lynch, Aoibhinn / Tarraga, Lluís / Larson, Eric B / Haapasalo, Annakaisa / Lawlor, Brian / Mosley, Thomas H / Lipton, Richard B / Solfrizzi, Vincenzo / Gill, Michael / Longstreth, W T / Montine, Thomas J / Frisardi, Vincenza / Diez-Fairen, Monica / Rivadeneira, Fernando / Petersen, Ronald C / Deramecourt, Vincent / Alvarez, Ignacio / Salani, Francesca / Ciaramella, Antonio / Boerwinkle, Eric / Reiman, Eric M / Fievet, Nathalie / Rotter, Jerome I / Reisch, Joan S / Hanon, Olivier / Cupidi, Chiara / Uitterlinden, A G Andre / Royall, Donald R / Dufouil, Carole / Maletta, Raffaele Giovanni / de Rojas, Itziar / Sano, Mary / Brice, Alexis / Cecchetti, Roberta / George-Hyslop, Peter St / Ritchie, Karen / Tsolaki, Magda / Tsuang, Debby W / Dubois, Bruno / Craig, David / Wu, Chuang-Kuo / Soininen, Hilkka / Avramidou, Despoina / Albin, Roger L / Fratiglioni, Laura / Germanou, Antonia / Apostolova, Liana G / Keller, Lina / Koutroumani, Maria / Arnold, Steven E / Panza, Francesco / Gkatzima, Olymbia / Asthana, Sanjay / Hannequin, Didier / Whitehead, Patrice / Atwood, Craig S / Caffarra, Paolo / Hampel, Harald / Quintela, Inés / Carracedo, Ángel / Lannfelt, Lars / Rubinsztein, David C / Barnes, Lisa L / Pasquier, Florence / Frölich, Lutz / Barral, Sandra / McGuinness, Bernadette / Beach, Thomas G / Johnston, Janet A / Becker, James T / Passmore, Peter / Bigio, Eileen H / Schott, Jonathan M / Bird, Thomas D / Warren, Jason D / Boeve, Bradley F / Lupton, Michelle K / Bowen, James D / Proitsi, Petra / Boxer, Adam / Powell, John F / Burke, James R / Kauwe, John S K / Burns, Jeffrey M / Mancuso, Michelangelo / Buxbaum, Joseph D / Bonuccelli, Ubaldo / Cairns, Nigel J / McQuillin, Andrew / Cao, Chuanhai / Livingston, Gill / Carlson, Chris S / Bass, Nicholas J / Carlsson, Cynthia M / Hardy, John / Carney, Regina M / Bras, Jose / Carrasquillo, Minerva M / Guerreiro, Rita / Allen, Mariet / Chui, Helena C / Fisher, Elizabeth / Masullo, Carlo / Crocco, Elizabeth A / DeCarli, Charles / Bisceglio, Gina / Dick, Malcolm / Ma, Li / Duara, Ranjan / Graff-Radford, Neill R / Evans, Denis A / Hodges, Angela / Faber, Kelley M / Scherer, Martin / Fallon, Kenneth B / Riemenschneider, Matthias / Fardo, David W / Heun, Reinhard / Farlow, Martin R / Kölsch, Heike / Ferris, Steven / Leber, Markus / Foroud, Tatiana M / Heuser, Isabella / Galasko, Douglas R / Giegling, Ina / Gearing, Marla / Hüll, Michael / Geschwind, Daniel H / Gilbert, John R / Morris, John / Green, Robert C / Mayo, Kevin / Growdon, John H / Feulner, Thomas / Hamilton, Ronald L / Harrell, Lindy E / Drichel, Dmitriy / Honig, Lawrence S / Cushion, Thomas D / Huentelman, Matthew J / Hollingworth, Paul / Hulette, Christine M / Hyman, Bradley T / Marshall, Rachel / Jarvik, Gail P / Meggy, Alun / Abner, Erin / Menzies, Georgina E / Jin, Lee-Way / Leonenko, Ganna / Real, Luis M / Jun, Gyungah R / Baldwin, Clinton T / Grozeva, Detelina / Karydas, Anna / Russo, Giancarlo / Kaye, Jeffrey A / Kim, Ronald / Jessen, Frank / Kowall, Neil W / Vellas, Bruno / Kramer, Joel H / Vardy, Emma / LaFerla, Frank M / Jöckel, Karl-Heinz / Lah, James J / Dichgans, Martin / Leverenz, James B / Mann, David / Levey, Allan I / Pickering-Brown, Stuart / Lieberman, Andrew P / Klopp, Norman / Lunetta, Kathryn L / Wichmann, H-Erich / Lyketsos, Constantine G / Morgan, Kevin / Marson, Daniel C / Brown, Kristelle / Martiniuk, Frank / Medway, Christopher / Mash, Deborah C / Nöthen, Markus M / Masliah, Eliezer / Hooper, Nigel M / McCormick, Wayne C / Daniele, Antonio / McCurry, Susan M / Bayer, Anthony / McDavid, Andrew N / Gallacher, John / McKee, Ann C / van den Bussche, Hendrik / Mesulam, Marsel / Brayne, Carol / Miller, Bruce L / Riedel-Heller, Steffi / Miller, Carol A / Miller, Joshua W / Al-Chalabi, Ammar / Morris, John C / Shaw, Christopher E / Myers, Amanda J / Wiltfang, Jens / O'Bryant, Sid / Olichney, John M / Alvarez, Victoria / Parisi, Joseph E / Singleton, Andrew B / Paulson, Henry L / Collinge, John / Perry, William R / Mead, Simon / Peskind, Elaine / Cribbs, David H / Rossor, Martin / Pierce, Aimee / Ryan, Natalie S / Poon, Wayne W / Nacmias, Benedetta / Potter, Huntington / Sorbi, Sandro / Quinn, Joseph F / Sacchinelli, Eleonora / Raj, Ashok / Spalletta, Gianfranco / Raskind, Murray / Caltagirone, Carlo / Bossù, Paola / Orfei, Maria Donata / Reisberg, Barry / Clarke, Robert / Reitz, Christiane / Smith, A David / Ringman, John M / Warden, Donald / Roberson, Erik D / Wilcock, Gordon / Rogaeva, Ekaterina / Bruni, Amalia Cecilia / Rosen, Howard J / Gallo, Maura / Rosenberg, Roger N / Ben-Shlomo, Yoav / Sager, Mark A / Mecocci, Patrizia / Saykin, Andrew J / Pastor, Pau / Cuccaro, Michael L / Vance, Jeffery M / Schneider, Julie A / Schneider, Lori S / Slifer, Susan / Seeley, William W / Smith, Amanda G / Sonnen, Joshua A / Spina, Salvatore / Stern, Robert A / Swerdlow, Russell H / Tang, Mitchell / Tanzi, Rudolph E / Trojanowski, John Q / Troncoso, Juan C / Van Deerlin, Vivianna M / Van Eldik, Linda J / Vinters, Harry V / Vonsattel, Jean Paul / Weintraub, Sandra / Welsh-Bohmer, Kathleen A / Wilhelmsen, Kirk C / Williamson, Jennifer / Wingo, Thomas S / Woltjer, Randall L / Wright, Clinton B / Yu, Chang-En / Yu, Lei / Saba, Yasaman / Pilotto, Alberto / Bullido, Maria J / Peters, Oliver / Crane, Paul K / Bennett, David / Bosco, Paola / Coto, Eliecer / Boccardi, Virginia / De Jager, Phil L / Lleo, Alberto / Warner, Nick / Lopez, Oscar L / Ingelsson, Martin / Deloukas, Panagiotis / Cruchaga, Carlos / Graff, Caroline / Gwilliam, Rhian / Fornage, Myriam / Goate, Alison M / Sanchez-Juan, Pascual / Kehoe, Patrick G / Amin, Najaf / Ertekin-Taner, Nilifur / Berr, Claudine / Debette, Stéphanie / Love, Seth / Launer, Lenore J / Younkin, Steven G / Dartigues, Jean-Francois / Corcoran, Chris / Ikram, M Arfan / Dickson, Dennis W / Nicolas, Gael / Campion, Dominique / Tschanz, JoAnn / Schmidt, Helena / Hakonarson, Hakon / Clarimon, Jordi / Munger, Ron / Schmidt, Reinhold / Farrer, Lindsay A / Van Broeckhoven, Christine / O'Donovan, Michael C / DeStefano, Anita L / Jones, Lesley / Haines, Jonathan L / Deleuze, Jean-Francois / Owen, Michael J / Gudnason, Vilmundur / Mayeux, Richard / Escott-Price, Valentina / Psaty, Bruce M / Ramirez, Alfredo / Wang, Li-San / Ruiz, Agustin / van Duijn, Cornelia M / Holmans, Peter A / Seshadri, Sudha / Williams, Julie / Amouyel, Phillippe / Schellenberg, Gerard D / Lambert, Jean-Charles / Pericak-Vance, Margaret A

Nature genetics

2019 Volume 51, Issue 9, Page(s) 1423–1424

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Language	English
Publishing date	2019-10-25
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-019-0495-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

Sims, Rebecca / van der Lee, Sven J / Naj, Adam C / Bellenguez, Céline / Badarinarayan, Nandini / Jakobsdottir, Johanna / Kunkle, Brian W / Boland, Anne / Raybould, Rachel / Bis, Joshua C / Martin, Eden R / Grenier-Boley, Benjamin / Heilmann-Heimbach, Stefanie / Chouraki, Vincent / Kuzma, Amanda B / Sleegers, Kristel / Vronskaya, Maria / Ruiz, Agustin / Graham, Robert R /

Olaso, Robert / Hoffmann, Per / Grove, Megan L / Vardarajan, Badri N / Hiltunen, Mikko / Nöthen, Markus M / White, Charles C / Hamilton-Nelson, Kara L / Epelbaum, Jacques / Maier, Wolfgang / Choi, Seung-Hoan / Beecham, Gary W / Dulary, Cécile / Herms, Stefan / Smith, Albert V / Funk, Cory C / Derbois, Céline / Forstner, Andreas J / Ahmad, Shahzad / Li, Hongdong / Bacq, Delphine / Harold, Denise / Satizabal, Claudia L / Valladares, Otto / Squassina, Alessio / Thomas, Rhodri / Brody, Jennifer A / Qu, Liming / Sánchez-Juan, Pascual / Morgan, Taniesha / Wolters, Frank J / Zhao, Yi / Garcia, Florentino Sanchez / Denning, Nicola / Fornage, Myriam / Malamon, John / Naranjo, Maria Candida Deniz / Majounie, Elisa / Mosley, Thomas H / Dombroski, Beth / Wallon, David / Lupton, Michelle K / Dupuis, Josée / Whitehead, Patrice / Fratiglioni, Laura / Medway, Christopher / Jian, Xueqiu / Mukherjee, Shubhabrata / Keller, Lina / Brown, Kristelle / Lin, Honghuang / Cantwell, Laura B / Panza, Francesco / McGuinness, Bernadette / Moreno-Grau, Sonia / Burgess, Jeremy D / Solfrizzi, Vincenzo / Proitsi, Petra / Adams, Hieab H / Allen, Mariet / Seripa, Davide / Pastor, Pau / Cupples, L Adrienne / Price, Nathan D / Hannequin, Didier / Frank-García, Ana / Levy, Daniel / Chakrabarty, Paramita / Caffarra, Paolo / Giegling, Ina / Beiser, Alexa S / Giedraitis, Vilmantas / Hampel, Harald / Garcia, Melissa E / Wang, Xue / Lannfelt, Lars / Mecocci, Patrizia / Eiriksdottir, Gudny / Crane, Paul K / Pasquier, Florence / Boccardi, Virginia / Henández, Isabel / Barber, Robert C / Scherer, Martin / Tarraga, Lluis / Adams, Perrie M / Leber, Markus / Chen, Yuning / Albert, Marilyn S / Riedel-Heller, Steffi / Emilsson, Valur / Beekly, Duane / Braae, Anne / Schmidt, Reinhold / Blacker, Deborah / Masullo, Carlo / Schmidt, Helena / Doody, Rachelle S / Spalletta, Gianfranco / Longstreth, W T / Fairchild, Thomas J / Bossù, Paola / Lopez, Oscar L / Frosch, Matthew P / Sacchinelli, Eleonora / Ghetti, Bernardino / Yang, Qiong / Huebinger, Ryan M / Jessen, Frank / Li, Shuo / Kamboh, M Ilyas / Morris, John / Sotolongo-Grau, Oscar / Katz, Mindy J / Corcoran, Chris / Dunstan, Melanie / Braddel, Amy / Thomas, Charlene / Meggy, Alun / Marshall, Rachel / Gerrish, Amy / Chapman, Jade / Aguilar, Miquel / Taylor, Sarah / Hill, Matt / Fairén, Mònica Díez / Hodges, Angela / Vellas, Bruno / Soininen, Hilkka / Kloszewska, Iwona / Daniilidou, Makrina / Uphill, James / Patel, Yogen / Hughes, Joseph T / Lord, Jenny / Turton, James / Hartmann, Annette M / Cecchetti, Roberta / Fenoglio, Chiara / Serpente, Maria / Arcaro, Marina / Caltagirone, Carlo / Orfei, Maria Donata / Ciaramella, Antonio / Pichler, Sabrina / Mayhaus, Manuel / Gu, Wei / Lleó, Alberto / Fortea, Juan / Blesa, Rafael / Barber, Imelda S / Brookes, Keeley / Cupidi, Chiara / Maletta, Raffaele Giovanni / Carrell, David / Sorbi, Sandro / Moebus, Susanne / Urbano, Maria / Pilotto, Alberto / Kornhuber, Johannes / Bosco, Paolo / Todd, Stephen / Craig, David / Johnston, Janet / Gill, Michael / Lawlor, Brian / Lynch, Aoibhinn / Fox, Nick C / Hardy, John / Albin, Roger L / Apostolova, Liana G / Arnold, Steven E / Asthana, Sanjay / Atwood, Craig S / Baldwin, Clinton T / Barnes, Lisa L / Barral, Sandra / Beach, Thomas G / Becker, James T / Bigio, Eileen H / Bird, Thomas D / Boeve, Bradley F / Bowen, James D / Boxer, Adam / Burke, James R / Burns, Jeffrey M / Buxbaum, Joseph D / Cairns, Nigel J / Cao, Chuanhai / Carlson, Chris S / Carlsson, Cynthia M / Carney, Regina M / Carrasquillo, Minerva M / Carroll, Steven L / Diaz, Carolina Ceballos / Chui, Helena C / Clark, David G / Cribbs, David H / Crocco, Elizabeth A / DeCarli, Charles / Dick, Malcolm / Duara, Ranjan / Evans, Denis A / Faber, Kelley M / Fallon, Kenneth B / Fardo, David W / Farlow, Martin R / Ferris, Steven / Foroud, Tatiana M / Galasko, Douglas R / Gearing, Marla / Geschwind, Daniel H / Gilbert, John R / Graff-Radford, Neill R / Green, Robert C / Growdon, John H / Hamilton, Ronald L / Harrell, Lindy E / Honig, Lawrence S / Huentelman, Matthew J / Hulette, Christine M / Hyman, Bradley T / Jarvik, Gail P / Abner, Erin / Jin, Lee-Way / Jun, Gyungah / Karydas, Anna / Kaye, Jeffrey A / Kim, Ronald / Kowall, Neil W / Kramer, Joel H / LaFerla, Frank M / Lah, James J / Leverenz, James B / Levey, Allan I / Li, Ge / Lieberman, Andrew P / Lunetta, Kathryn L / Lyketsos, Constantine G / Marson, Daniel C / Martiniuk, Frank / Mash, Deborah C / Masliah, Eliezer / McCormick, Wayne C / McCurry, Susan M / McDavid, Andrew N / McKee, Ann C / Mesulam, Marsel / Miller, Bruce L / Miller, Carol A / Miller, Joshua W / Morris, John C / Murrell, Jill R / Myers, Amanda J / O'Bryant, Sid / Olichney, John M / Pankratz, Vernon S / Parisi, Joseph E / Paulson, Henry L / Perry, William / Peskind, Elaine / Pierce, Aimee / Poon, Wayne W / Potter, Huntington / Quinn, Joseph F / Raj, Ashok / Raskind, Murray / Reisberg, Barry / Reitz, Christiane / Ringman, John M / Roberson, Erik D / Rogaeva, Ekaterina / Rosen, Howard J / Rosenberg, Roger N / Sager, Mark A / Saykin, Andrew J / Schneider, Julie A / Schneider, Lon S / Seeley, William W / Smith, Amanda G / Sonnen, Joshua A / Spina, Salvatore / Stern, Robert A / Swerdlow, Russell H / Tanzi, Rudolph E / Thornton-Wells, Tricia A / Trojanowski, John Q / Troncoso, Juan C / Van Deerlin, Vivianna M / Van Eldik, Linda J / Vinters, Harry V / Vonsattel, Jean Paul / Weintraub, Sandra / Welsh-Bohmer, Kathleen A / Wilhelmsen, Kirk C / Williamson, Jennifer / Wingo, Thomas S / Woltjer, Randall L / Wright, Clinton B / Yu, Chang-En / Yu, Lei / Garzia, Fabienne / Golamaully, Feroze / Septier, Gislain / Engelborghs, Sebastien / Vandenberghe, Rik / De Deyn, Peter P / Fernadez, Carmen Muñoz / Benito, Yoland Aladro / Thonberg, Hakan / Forsell, Charlotte / Lilius, Lena / Kinhult-Stählbom, Anne / Kilander, Lena / Brundin, RoseMarie / Concari, Letizia / Helisalmi, Seppo / Koivisto, Anne Maria / Haapasalo, Annakaisa / Dermecourt, Vincent / Fievet, Nathalie / Hanon, Olivier / Dufouil, Carole / Brice, Alexis / Ritchie, Karen / Dubois, Bruno / Himali, Jayanadra J / Keene, C Dirk / Tschanz, JoAnn / Fitzpatrick, Annette L / Kukull, Walter A / Norton, Maria / Aspelund, Thor / Larson, Eric B / Munger, Ron / Rotter, Jerome I / Lipton, Richard B / Bullido, María J / Hofman, Albert / Montine, Thomas J / Coto, Eliecer / Boerwinkle, Eric / Petersen, Ronald C / Alvarez, Victoria / Rivadeneira, Fernando / Reiman, Eric M / Gallo, Maura / O'Donnell, Christopher J / Reisch, Joan S / Bruni, Amalia Cecilia / Royall, Donald R / Dichgans, Martin / Sano, Mary / Galimberti, Daniela / St George-Hyslop, Peter / Scarpini, Elio / Tsuang, Debby W / Mancuso, Michelangelo / Bonuccelli, Ubaldo / Winslow, Ashley R / Daniele, Antonio / Wu, Chuang-Kuo / Peters, Oliver / Nacmias, Benedetta / Riemenschneider, Matthias / Heun, Reinhard / Brayne, Carol / Rubinsztein, David C / Bras, Jose / Guerreiro, Rita / Al-Chalabi, Ammar / Shaw, Christopher E / Collinge, John / Mann, David / Tsolaki, Magda / Clarimón, Jordi / Sussams, Rebecca / Lovestone, Simon / O'Donovan, Michael C / Owen, Michael J / Behrens, Timothy W / Mead, Simon / Goate, Alison M / Uitterlinden, Andre G / Holmes, Clive / Cruchaga, Carlos / Ingelsson, Martin / Bennett, David A / Powell, John / Golde, Todd E / Graff, Caroline / De Jager, Philip L / Morgan, Kevin / Ertekin-Taner, Nilufer / Combarros, Onofre / Psaty, Bruce M / Passmore, Peter / Younkin, Steven G / Berr, Claudine / Gudnason, Vilmundur / Rujescu, Dan / Dickson, Dennis W / Dartigues, Jean-François / DeStefano, Anita L / Ortega-Cubero, Sara / Hakonarson, Hakon / Campion, Dominique / Boada, Merce / Kauwe, John Keoni / Farrer, Lindsay A / Van Broeckhoven, Christine / Ikram, M Arfan / Jones, Lesley / Haines, Jonathan L / Tzourio, Christophe / Launer, Lenore J / Escott-Price, Valentina / Mayeux, Richard / Deleuze, Jean-François / Amin, Najaf / Holmans, Peter A / Pericak-Vance, Margaret A / Amouyel, Philippe / van Duijn, Cornelia M / Ramirez, Alfredo / Wang, Li-San / Lambert, Jean-Charles / Seshadri, Sudha / Williams, Julie / Schellenberg, Gerard D

Nature genetics

2017 Volume 49, Issue 9, Page(s) 1373–1384

Abstract: 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 × ... ...

Abstract	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
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Alzheimer Disease/genetics ; Amino Acid Sequence ; Case-Control Studies ; Exome/genetics ; Gene Expression Profiling ; Gene Frequency ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Immunity, Innate/genetics ; Linkage Disequilibrium ; Membrane Glycoproteins/genetics ; Microglia/metabolism ; Odds Ratio ; Phospholipase C gamma/genetics ; Polymorphism, Single Nucleotide ; Protein Interaction Maps/genetics ; Receptors, Immunologic/genetics ; Sequence Homology, Amino Acid
Chemical Substances	ABI3 protein, human ; Adaptor Proteins, Signal Transducing ; Membrane Glycoproteins ; Receptors, Immunologic ; TREM2 protein, human ; Phospholipase C gamma (EC 3.1.4.3)
Language	English
Publishing date	2017-07-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/ng.3916
Database	MEDical Literature Analysis and Retrieval System OnLINE

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