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Author: Jean-Charles Lambert (110)


Nov
2017

We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk and rare variants in SORL1, TREM2, and ABCA7.

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Oct
2017

Bridging integrator 1 (bin1) gene is a genetic determinant of Alzheimer's disease (AD) and has been reported to modulate Alzheimer's pathogenesis through pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction as well as the molecular details of this interaction are still not fully resolved. As a consequence, how BIN1 through its interaction with Tau affects AD risk is also still not determined.

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Dec
1969

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

Nat Genet 2017 09 17;49(9):1373-1384. Epub 2017 Jul 17.
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, 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.

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Aug
2017

A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages.

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Dec
1969

Corrigendum: 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

Sci Rep 2017 05 26;7:46835. Epub 2017 May 26.
Mathias Gorski, Peter J van der Most, Alexander Teumer, Audrey Y Chu, Man Li, Vladan Mijatovic, Ilja M Nolte, Massimiliano Cocca, Daniel Taliun, Felicia Gomez, Yong Li, Bamidele Tayo, Adrienne Tin, Mary F Feitosa, Thor Aspelund, John Attia, Reiner Biffar, Murielle Bochud, Eric Boerwinkle, Ingrid Borecki, Erwin P Bottinger, Ming-Huei Chen, Vincent Chouraki, Marina Ciullo, Josef Coresh, Marilyn C Cornelis, Gary C Curhan, Adamo Pio d' Adamo, Abbas Dehghan, Laura Dengler, Jingzhong Ding, Gudny Eiriksdottir, Karlhans Endlich, Stefan Enroth, Tõnu Esko, Oscar H Franco, Paolo Gasparini, Christian Gieger, Giorgia Girotto, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, Stephen J Hancock, Tamara B Harris, Catherine Helmer, Simon Höllerer, Edith Hofer, Albert Hofman, Elizabeth G Holliday, Georg Homuth, Frank B Hu, Cornelia Huth, Nina Hutri-Kähönen, Shih-Jen Hwang, Medea Imboden, Åsa Johansson, Mika Kähönen, Wolfgang König, Holly Kramer, Bernhard K Krämer, Ashish Kumar, Zoltan Kutalik, Jean-Charles Lambert, Lenore J Launer, Terho Lehtimäki, Martin H de Borst, Gerjan Navis, Morris Swertz, Yongmei Liu, Kurt Lohman, Ruth J F Loos, Yingchang Lu, Leo-Pekka Lyytikäinen, Mark A McEvoy, Christa Meisinger, Thomas Meitinger, Andres Metspalu, Marie Metzger, Evelin Mihailov, Paul Mitchell, Matthias Nauck, Albertine J Oldehinkel, Matthias Olden, Brenda Wjh Penninx, Giorgio Pistis, Peter P Pramstaller, Nicole Probst-Hensch, Olli T Raitakari, Rainer Rettig, Paul M Ridker, Fernando Rivadeneira, Antonietta Robino, Sylvia E Rosas, Douglas Ruderfer, Daniela Ruggiero, Yasaman Saba, Cinzia Sala, Helena Schmidt, Reinhold Schmidt, Rodney J Scott, Sanaz Sedaghat, Albert V Smith, Rossella Sorice, Benedicte Stengel, Sylvia Stracke, Konstantin Strauch, Daniela Toniolo, Andre G Uitterlinden, Sheila Ulivi, Jorma S Viikari, Uwe Völker, Peter Vollenweider, Henry Völzke, Dragana Vuckovic, Melanie Waldenberger, Jie Jin Wang, Qiong Yang, Daniel I Chasman, Gerard Tromp, Harold Snieder, Iris M Heid, Caroline S Fox, Anna Köttgen, Cristian Pattaro, Carsten A Böger, Christian Fuchsberger
This corrects the article DOI: 10.1038/srep45040.

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Dec
1969

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

Sci Rep 2017 04 28;7:45040. Epub 2017 Apr 28.
Mathias Gorski, Peter J van der Most, Alexander Teumer, Audrey Y Chu, Man Li, Vladan Mijatovic, Ilja M Nolte, Massimiliano Cocca, Daniel Taliun, Felicia Gomez, Yong Li, Bamidele Tayo, Adrienne Tin, Mary F Feitosa, Thor Aspelund, John Attia, Reiner Biffar, Murielle Bochud, Eric Boerwinkle, Ingrid Borecki, Erwin P Bottinger, Ming-Huei Chen, Vincent Chouraki, Marina Ciullo, Josef Coresh, Marilyn C Cornelis, Gary C Curhan, Adamo Pio d'Adamo, Abbas Dehghan, Laura Dengler, Jingzhong Ding, Gudny Eiriksdottir, Karlhans Endlich, Stefan Enroth, Tõnu Esko, Oscar H Franco, Paolo Gasparini, Christian Gieger, Giorgia Girotto, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, Stephen J Hancock, Tamara B Harris, Catherine Helmer, Simon Höllerer, Edith Hofer, Albert Hofman, Elizabeth G Holliday, Georg Homuth, Frank B Hu, Cornelia Huth, Nina Hutri-Kähönen, Shih-Jen Hwang, Medea Imboden, Åsa Johansson, Mika Kähönen, Wolfgang König, Holly Kramer, Bernhard K Krämer, Ashish Kumar, Zoltan Kutalik, Jean-Charles Lambert, Lenore J Launer, Terho Lehtimäki, Martin de Borst, Gerjan Navis, Morris Swertz, Yongmei Liu, Kurt Lohman, Ruth J F Loos, Yingchang Lu, Leo-Pekka Lyytikäinen, Mark A McEvoy, Christa Meisinger, Thomas Meitinger, Andres Metspalu, Marie Metzger, Evelin Mihailov, Paul Mitchell, Matthias Nauck, Albertine J Oldehinkel, Matthias Olden, Brenda Wjh Penninx, Giorgio Pistis, Peter P Pramstaller, Nicole Probst-Hensch, Olli T Raitakari, Rainer Rettig, Paul M Ridker, Fernando Rivadeneira, Antonietta Robino, Sylvia E Rosas, Douglas Ruderfer, Daniela Ruggiero, Yasaman Saba, Cinzia Sala, Helena Schmidt, Reinhold Schmidt, Rodney J Scott, Sanaz Sedaghat, Albert V Smith, Rossella Sorice, Benedicte Stengel, Sylvia Stracke, Konstantin Strauch, Daniela Toniolo, Andre G Uitterlinden, Sheila Ulivi, Jorma S Viikari, Uwe Völker, Peter Vollenweider, Henry Völzke, Dragana Vuckovic, Melanie Waldenberger, Jie Jin Wang, Qiong Yang, Daniel I Chasman, Gerard Tromp, Harold Snieder, Iris M Heid, Caroline S Fox, Anna Köttgen, Cristian Pattaro, Carsten A Böger, Christian Fuchsberger
HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data.

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Jan
2017

Tau-mediated neurodegeneration in Alzheimer's disease and tauopathies is generally assumed to start in a normally developed brain. However, several lines of evidence suggest that impaired Tau isoform expression during development could affect mitosis and ploidy in post-mitotic differentiated tissue. Interestingly, the relative expression levels of Tau isoforms containing either 3 (3R-Tau) or 4 repeats (4R-Tau) play an important role both during brain development and neurodegeneration.

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Jun
2017

Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer's disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the "post-GWAS" era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective.

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Jun
2016

Effective prevention of Alzheimer's disease (AD) requires the development of risk prediction tools permitting preclinical intervention. We constructed a genetic risk score (GRS) comprising common genetic variants associated with AD, evaluated its association with incident AD and assessed its capacity to improve risk prediction over traditional models based on age, sex, education, and APOEɛ4. In eight prospective cohorts included in the International Genomics of Alzheimer's Project (IGAP), we derived weighted sum of risk alleles from the 19 top SNPs reported by the IGAP GWAS in participants aged 65 and older without prevalent dementia.

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Jul
2016

Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion.

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Jun
2016

Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.

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May
2016

A growing body of evidence suggests that microRNAs (miRNAs) are involved in Alzheimer's disease (AD) and that some disease-associated genetic variants are located within miRNA binding sites. In the present study, we sought to characterize functional polymorphisms in miRNA target sites within the loci defined in earlier genome-wide association studies (GWAS). The main objectives of this study were to (1) facilitate the identification of the gene or genes responsible for the GWAS signal within a locus of interest and (2) determine how functional polymorphisms might be involved in the AD process (e.

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Jun
2016

To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting.
We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls.
After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.

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May
2016

A growing body of research has examined the relationship between episodic memory decline, the cognitive hallmark of Alzheimer's disease (AD), and the presence of Apolipoprotein E ε4 (APOE ε4) allele, a major genetic risk factor for the disease. Our review attempts to summarize and critically evaluate this literature. We performed a systematic search for studies assessing episodic memory in AD patients who were genotyped for APOE ε4 and identified fourteen papers.

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Jan
2016

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Nat Commun 2016 Jan 21;7:10023. Epub 2016 Jan 21.
Cristian Pattaro, Alexander Teumer, Mathias Gorski, Audrey Y Chu, Man Li, Vladan Mijatovic, Maija Garnaas, Adrienne Tin, Rossella Sorice, Yong Li, Daniel Taliun, Matthias Olden, Meredith Foster, Qiong Yang, Ming-Huei Chen, Tune H Pers, Andrew D Johnson, Yi-An Ko, Christian Fuchsberger, Bamidele Tayo, Michael Nalls, Mary F Feitosa, Aaron Isaacs, Abbas Dehghan, Pio d'Adamo, Adebowale Adeyemo, Aida Karina Dieffenbach, Alan B Zonderman, Ilja M Nolte, Peter J van der Most, Alan F Wright, Alan R Shuldiner, Alanna C Morrison, Albert Hofman, Albert V Smith, Albert W Dreisbach, Andre Franke, Andre G Uitterlinden, Andres Metspalu, Anke Tonjes, Antonio Lupo, Antonietta Robino, Åsa Johansson, Ayse Demirkan, Barbara Kollerits, Barry I Freedman, Belen Ponte, Ben A Oostra, Bernhard Paulweber, Bernhard K Krämer, Braxton D Mitchell, Brendan M Buckley, Carmen A Peralta, Caroline Hayward, Catherine Helmer, Charles N Rotimi, Christian M Shaffer, Christian Müller, Cinzia Sala, Cornelia M van Duijn, Aude Saint-Pierre, Daniel Ackermann, Daniel Shriner, Daniela Ruggiero, Daniela Toniolo, Yingchang Lu, Daniele Cusi, Darina Czamara, David Ellinghaus, David S Siscovick, Douglas Ruderfer, Christian Gieger, Harald Grallert, Elena Rochtchina, Elizabeth J Atkinson, Elizabeth G Holliday, Eric Boerwinkle, Erika Salvi, Erwin P Bottinger, Federico Murgia, Fernando Rivadeneira, Florian Ernst, Florian Kronenberg, Frank B Hu, Gerjan J Navis, Gary C Curhan, George B Ehret, Georg Homuth, Stefan Coassin, Gian-Andri Thun, Giorgio Pistis, Giovanni Gambaro, Giovanni Malerba, Grant W Montgomery, Gudny Eiriksdottir, Gunnar Jacobs, Guo Li, H-Erich Wichmann, Harry Campbell, Helena Schmidt, Henri Wallaschofski, Henry Völzke, Hermann Brenner, Heyo K Kroemer, Holly Kramer, Honghuang Lin, I Mateo Leach, Ian Ford, Idris Guessous, Igor Rudan, Inga Prokopenko, Ingrid Borecki, Iris M Heid, Ivana Kolcic, Ivana Persico, J Wouter Jukema, James F Wilson, Janine F Felix, Jasmin Divers, Jean-Charles Lambert, Jeanette M Stafford, Jean-Michel Gaspoz, Jennifer A Smith, Jessica D Faul, Jie Jin Wang, Jingzhong Ding, Joel N Hirschhorn, John Attia, John B Whitfield, John Chalmers, Jorma Viikari, Josef Coresh, Joshua C Denny, Juha Karjalainen, Jyotika K Fernandes, Karlhans Endlich, Katja Butterbach, Keith L Keene, Kurt Lohman, Laura Portas, Lenore J Launer, Leo-Pekka Lyytikäinen, Loic Yengo, Lude Franke, Luigi Ferrucci, Lynda M Rose, Lyudmyla Kedenko, Madhumathi Rao, Maksim Struchalin, Marcus E Kleber, Margherita Cavalieri, Margot Haun, Marilyn C Cornelis, Marina Ciullo, Mario Pirastu, Mariza de Andrade, Mark A McEvoy, Mark Woodward, Martin Adam, Massimiliano Cocca, Matthias Nauck, Medea Imboden, Melanie Waldenberger, Menno Pruijm, Marie Metzger, Michael Stumvoll, Michele K Evans, Michele M Sale, Mika Kähönen, Mladen Boban, Murielle Bochud, Myriam Rheinberger, Niek Verweij, Nabila Bouatia-Naji, Nicholas G Martin, Nick Hastie, Nicole Probst-Hensch, Nicole Soranzo, Olivier Devuyst, Olli Raitakari, Omri Gottesman, Oscar H Franco, Ozren Polasek, Paolo Gasparini, Patricia B Munroe, Paul M Ridker, Paul Mitchell, Paul Muntner, Christa Meisinger, Johannes H Smit, , , , , , Peter Kovacs, Philipp S Wild, Philippe Froguel, Rainer Rettig, Reedik Mägi, Reiner Biffar, Reinhold Schmidt, Rita P S Middelberg, Robert J Carroll, Brenda W Penninx, Rodney J Scott, Ronit Katz, Sanaz Sedaghat, Sarah H Wild, Sharon L R Kardia, Sheila Ulivi, Shih-Jen Hwang, Stefan Enroth, Stefan Kloiber, Stella Trompet, Benedicte Stengel, Stephen J Hancock, Stephen T Turner, Sylvia E Rosas, Sylvia Stracke, Tamara B Harris, Tanja Zeller, Tatijana Zemunik, Terho Lehtimäki, Thomas Illig, Thor Aspelund, Tiit Nikopensius, Tonu Esko, Toshiko Tanaka, Ulf Gyllensten, Uwe Völker, Valur Emilsson, Veronique Vitart, Ville Aalto, Vilmundur Gudnason, Vincent Chouraki, Wei-Min Chen, Wilmar Igl, Winfried März, Wolfgang Koenig, Wolfgang Lieb, Ruth J F Loos, Yongmei Liu, Harold Snieder, Peter P Pramstaller, Afshin Parsa, Jeffrey R O'Connell, Katalin Susztak, Pavel Hamet, Johanne Tremblay, Ian H de Boer, Carsten A Böger, Wolfram Goessling, Daniel I Chasman, Anna Köttgen, W H Linda Kao, Caroline S Fox
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci.

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Mar
2016

Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

Diabetes 2016 Mar 2;65(3):803-17. Epub 2015 Dec 2.
Alexander Teumer, Adrienne Tin, Rossella Sorice, Mathias Gorski, Nan Cher Yeo, Audrey Y Chu, Man Li, Yong Li, Vladan Mijatovic, Yi-An Ko, Daniel Taliun, Alessandro Luciani, Ming-Huei Chen, Qiong Yang, Meredith C Foster, Matthias Olden, Linda T Hiraki, Bamidele O Tayo, Christian Fuchsberger, Aida Karina Dieffenbach, Alan R Shuldiner, Albert V Smith, Allison M Zappa, Antonio Lupo, Barbara Kollerits, Belen Ponte, Bénédicte Stengel, Bernhard K Krämer, Bernhard Paulweber, Braxton D Mitchell, Caroline Hayward, Catherine Helmer, Christa Meisinger, Christian Gieger, Christian M Shaffer, Christian Müller, Claudia Langenberg, Daniel Ackermann, David Siscovick, , Eric Boerwinkle, Florian Kronenberg, Georg B Ehret, Georg Homuth, Gerard Waeber, Gerjan Navis, Giovanni Gambaro, Giovanni Malerba, Gudny Eiriksdottir, Guo Li, H Erich Wichmann, Harald Grallert, Henri Wallaschofski, Henry Völzke, Herrmann Brenner, Holly Kramer, I Mateo Leach, Igor Rudan, Hans L Hillege, Jacques S Beckmann, Jean Charles Lambert, Jian'an Luan, Jing Hua Zhao, John Chalmers, Josef Coresh, Joshua C Denny, Katja Butterbach, Lenore J Launer, Luigi Ferrucci, Lyudmyla Kedenko, Margot Haun, Marie Metzger, Mark Woodward, Matthew J Hoffman, Matthias Nauck, Melanie Waldenberger, Menno Pruijm, Murielle Bochud, Myriam Rheinberger, Niek Verweij, Nicholas J Wareham, Nicole Endlich, Nicole Soranzo, Ozren Polasek, Pim van der Harst, Peter Paul Pramstaller, Peter Vollenweider, Philipp S Wild, Ron T Gansevoort, Rainer Rettig, Reiner Biffar, Robert J Carroll, Ronit Katz, Ruth J F Loos, Shih-Jen Hwang, Stefan Coassin, Sven Bergmann, Sylvia E Rosas, Sylvia Stracke, Tamara B Harris, Tanguy Corre, Tanja Zeller, Thomas Illig, Thor Aspelund, Toshiko Tanaka, Uwe Lendeckel, Uwe Völker, Vilmundur Gudnason, Vincent Chouraki, Wolfgang Koenig, Zoltan Kutalik, Jeffrey R O'Connell, Afshin Parsa, Iris M Heid, Andrew D Paterson, Ian H de Boer, Olivier Devuyst, Jozef Lazar, Karlhans Endlich, Katalin Susztak, Johanne Tremblay, Pavel Hamet, Howard J Jacob, Carsten A Böger, Caroline S Fox, Cristian Pattaro, Anna Köttgen
Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.

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Dec
2015

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).

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Sep
2015

The application of high-throughput genomic approaches has revealed 24 novel risk loci for Alzheimer's disease (AD). We recently reported that the bridging integrator 1 (BIN1) risk gene is linked to Tau pathology.
We used glutathione S-transferase pull-down assays and nuclear magnetic resonance (NMR) experiments to demonstrate that BIN1 and Tau proteins interact directly and then map the interaction between BIN1's SH3 domain and Tau's proline-rich domain (PRD) .

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Jan
2016

Aβ-related cerebral amyloid angiopathy (CAA) is a major cause of primary non-traumatic brain hemorrhage. In families with an early onset of the disease, CAA can be due to amyloid precursor protein (APP) pathogenic variants or duplications. APP duplications lead to a ~1.

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May
2015

Genome-wide association study of kidney function decline in individuals of European descent.

Kidney Int 2015 May 10;87(5):1017-29. Epub 2014 Dec 10.
Mathias Gorski, Adrienne Tin, Maija Garnaas, Gearoid M McMahon, Audrey Y Chu, Bamidele O Tayo, Cristian Pattaro, Alexander Teumer, Daniel I Chasman, John Chalmers, Pavel Hamet, Johanne Tremblay, Marc Woodward, Thor Aspelund, Gudny Eiriksdottir, Vilmundur Gudnason, Tamara B Harris, Lenore J Launer, Albert V Smith, Braxton D Mitchell, Jeffrey R O'Connell, Alan R Shuldiner, Josef Coresh, Man Li, Paul Freudenberger, Edith Hofer, Helena Schmidt, Reinhold Schmidt, Elizabeth G Holliday, Paul Mitchell, Jie Jin Wang, Ian H de Boer, Guo Li, David S Siscovick, Zoltan Kutalik, Tanguy Corre, Peter Vollenweider, Gérard Waeber, Jayanta Gupta, Peter A Kanetsky, Shih-Jen Hwang, Matthias Olden, Qiong Yang, Mariza de Andrade, Elizabeth J Atkinson, Sharon L R Kardia, Stephen T Turner, Jeanette M Stafford, Jingzhong Ding, Yongmei Liu, Cristina Barlassina, Daniele Cusi, Erika Salvi, Jan A Staessen, Paul M Ridker, Harald Grallert, Christa Meisinger, Martina Müller-Nurasyid, Bernhard K Krämer, Holly Kramer, Sylvia E Rosas, Ilja M Nolte, Brenda W Penninx, Harold Snieder, M Fabiola Del Greco, Andre Franke, Ute Nöthlings, Wolfgang Lieb, Stephan J L Bakker, Ron T Gansevoort, Pim van der Harst, Abbas Dehghan, Oscar H Franco, Albert Hofman, Fernando Rivadeneira, Sanaz Sedaghat, André G Uitterlinden, Stefan Coassin, Margot Haun, Barbara Kollerits, Florian Kronenberg, Bernhard Paulweber, Nicole Aumann, Karlhans Endlich, Mike Pietzner, Uwe Völker, Rainer Rettig, Vincent Chouraki, Catherine Helmer, Jean-Charles Lambert, Marie Metzger, Benedicte Stengel, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Olli Raitakari, Andrew Johnson, Afshin Parsa, Murielle Bochud, Iris M Heid, Wolfram Goessling, Anna Köttgen, W H Linda Kao, Caroline S Fox, Carsten A Böger
Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR.

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Feb
2015

The human TAR DNA binding protein 43 (TDP-43), encoded by the gene TARDBP, plays a central role in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP-43 inclusions are also found in up to approximately 60% of Alzheimer's disease (AD) brains. Although ALS-causing TARDBP mutations cluster in the C-terminal glycine-rich region of the protein, the pathogenic nature of the atypical missense variants p.

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Mar
2015

Plasma amyloid-β (Aβ) peptide levels have been examined as a low-cost accessible marker for risk of incident Alzheimer's disease (AD) and dementia, but results have varied between studies. We reassessed these associations in one of the largest, prospective, community-based studies to date.
A total of 2189 dementia-free, Framingham Study participants aged >60 years (mean age, 72 ± 8 years; 56% women) had plasma Aβ1-42 and Aβ1-40 measured and were followed prospectively (mean, 7.

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Dec
1969

Despite the growing number of genome-wide association studies, the involvement of polymorphisms in microRNA target sites (polymiRTS) in Alzheimer's disease (AD) remains poorly investigated. Recently, we have shown that AD-associated single-nucleotide polymorphisms (SNPs) present in the 3' untranslated region (3'UTR) of amyloid precursor protein (APP) could directly affect miRNA function. In theory, loss of microRNA (miRNA) function could lead to risk for AD by increasing APP expression and Aβ peptide production.

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Dec
1969

The worldwide population is ageing and the proportion of elderly aged 60 and over is expected to dramatically rise in Low and Middle Income Countries (LMIC). The epidemic of dementia will not spare those countries, where the largest increases in numbers of people affected are estimated. Besides, dementia is still understudied in sub-Saharan Africa (SSA) compared to other regions.

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Jun
2015

We evaluated if plasma β-amyloid (Aβ) levels were associated with mortality risks in a subsample of the French Three-City (3C) prospective cohort study.
Analyses were based on 1254 participants randomly selected from the initial 3C cohort stratified by center, sex, and age in the context of a nested case-cohort study to investigate biological variables. Associations between plasma Aβ and mortality were assessed with the Cox regression model with delayed entry including various potential confounding factors and testing possible mediators.

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Nov
2014

We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer's disease (AD) (2259 patients and 6017 controls from France). Particularly, in the exhaustive genome-wide epistasis screening we identified AD-associated interacting SNPs-pair from chromosome 6q11.

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Dec
1969

Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

PLoS One 2014 12;9(6):e94661. Epub 2014 Jun 12.
Valentina Escott-Price, Céline Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L DeStefano, Jean-Charles Lambert, Carla A Ibrahim-Verbaas, Adam C Naj, Rebecca Sims, Gyungah Jun, Joshua C Bis, Gary W Beecham, Benjamin Grenier-Boley, Giancarlo Russo, Tricia A Thornton-Wells, Nicola Denning, Albert V Smith, Vincent Chouraki, Charlene Thomas, M Arfan Ikram, Diana Zelenika, Badri N Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L Dunstan, Maria Vronskaya, , Andrew D Johnson, Agustin Ruiz, Marie-Thérèse Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L Lopez, Philip L De Jager, Vincent Deramecourt, Janet A Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M Goate, Nathalie Fiévet, Matthew J Huentelman, Michael Gill, Kristelle Brown, M Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B Larson, Amanda J Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimon, Alberto Lleo, Anthony Bayer, Debby W Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G Younkin, Eliecer Coto, Kara L Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J Owen, Kelley M Faber, Palmi V Jonsson, Onofre Combarros, Michael C O'Donovan, Laura B Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H Mosley, David A Bennett, Tamara B Harris, Laura Fratiglioni, Clive Holmes, Renee F A G de Bruijn, Peter Passmore, Thomas J Montine, Karolien Bettens, Jerome I Rotter, Alexis Brice, Kevin Morgan, Tatiana M Foroud, Walter A Kukull, Didier Hannequin, John F Powell, Michael A Nalls, Karen Ritchie, Kathryn L Lunetta, John S K Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R Martin, Reinhold Schmidt, Dan Rujescu, Jean-François Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M Nöthen, Caroline Graff, Bruce M Psaty, Jonathan L Haines, Mark Lathrop, Margaret A Pericak-Vance, Lenore J Launer, Christine Van Broeckhoven, Lindsay A Farrer, Cornelia M van Duijn, Alfredo Ramirez, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams,
Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.

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Dec
1969

Several genes implicated in high-density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations.

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Feb
2014

We investigated the relationship of anthropometric markers of obesity with quantitative magnetic resonance imaging markers of brain aging, including measures of total brain volume (TBV), gray matter volume (GMV), hippocampal volume, white matter hyperintensity volume (WMHV), and brain infarcts, and examined causality using Mendelian randomization (MR). Analyses were performed in 1779 individuals (60.4% women, 72.

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Dec
2013

Recognition of the well-known pleiotropism of autoimmune genes supports the concept of a shared pathogenesis across autoimmune diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). Studies have reproducibly demonstrated an association between susceptibility to RA and polymorphisms of the CCR6 gene, a surface marker for Th17 cells, and the causal variant was recently identified. The present study was thus undertaken to investigate whether CCR6 polymorphisms could also be associated with susceptibility to SSc.

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Jul
2013

Venous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a two-stage genome-wide association study (GWAS) among individuals of European ancestry in the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) VTE consortium.

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Mar
2013

Venous Thrombosis (VT) is a common multifactorial disease with an estimated heritability between 35% and 60%. Known genetic polymorphisms identified so far only explain ~5% of the genetic variance of the disease. This study was aimed to investigate whether pair-wise interactions between common single nucleotide polymorphisms (SNPs) could exist and modulate the risk of VT.

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May
2013

Pulmonary arterial hypertension (PAH) is a rare, severe disease resulting from progressive obliteration of small-caliber pulmonary arteries by proliferating vascular cells. PAH can occur without recognized etiology (idiopathic PAH), be associated with a systemic disease or occur as a heritable form, with BMPR2 mutated in approximately 80% of familial and 15% of idiopathic PAH cases. We conducted a genome-wide association study (GWAS) based on 2 independent case-control studies for idiopathic and familial PAH (without BMPR2 mutations), including a total of 625 cases and 1,525 healthy individuals.

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Jun
2013

The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD).

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Jan
2013

TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43) in Drosophila.

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Jan
2013

Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.
We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease.

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Dec
1969

Studies of plasma amyloid-β (Aβ) levels as potential biomarkers for incident Alzheimer's disease (AD) have yielded contradictory results. We explored the associations between plasma Aβ(40), Aβ(42), and truncated Aβ levels, and prognosis of dementia in participants of the prospective 3-City Study. 120 aged individuals diagnosed with 2-year incident dementia were followed up for seven years.

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Dec
2012

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

Hum Mol Genet 2012 Dec 8;21(24):5329-43. Epub 2012 Sep 8.
Daniel I Chasman, Christian Fuchsberger, Cristian Pattaro, Alexander Teumer, Carsten A Böger, Karlhans Endlich, Matthias Olden, Ming-Huei Chen, Adrienne Tin, Daniel Taliun, Man Li, Xiaoyi Gao, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C Foster, Conall M O'Seaghdha, Nicole Glazer, Aaron Isaacs, Ching-Ti Liu, Albert V Smith, Jeffrey R O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Andrew D Johnson, Hinco J Gierman, Mary F Feitosa, Shih-Jen Hwang, Elizabeth J Atkinson, Kurt Lohman, Marilyn C Cornelis, Asa Johansson, Anke Tönjes, Abbas Dehghan, Jean-Charles Lambert, Elizabeth G Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimäki, Tõnu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y Chu, Federico Murgia, Stella Trompet, Medea Imboden, Stefan Coassin, Giorgio Pistis, , , , , Tamara B Harris, Lenore J Launer, Thor Aspelund, Gudny Eiriksdottir, Braxton D Mitchell, Eric Boerwinkle, Helena Schmidt, Margherita Cavalieri, Madhumathi Rao, Frank Hu, Ayse Demirkan, Ben A Oostra, Mariza de Andrade, Stephen T Turner, Jingzhong Ding, Jeanette S Andrews, Barry I Freedman, Franco Giulianini, Wolfgang Koenig, Thomas Illig, Christa Meisinger, Christian Gieger, Lina Zgaga, Tatijana Zemunik, Mladen Boban, Cosetta Minelli, Heather E Wheeler, Wilmar Igl, Ghazal Zaboli, Sarah H Wild, Alan F Wright, Harry Campbell, David Ellinghaus, Ute Nöthlings, Gunnar Jacobs, Reiner Biffar, Florian Ernst, Georg Homuth, Heyo K Kroemer, Matthias Nauck, Sylvia Stracke, Uwe Völker, Henry Völzke, Peter Kovacs, Michael Stumvoll, Reedik Mägi, Albert Hofman, Andre G Uitterlinden, Fernando Rivadeneira, Yurii S Aulchenko, Ozren Polasek, Nick Hastie, Veronique Vitart, Catherine Helmer, Jie Jin Wang, Bénédicte Stengel, Daniela Ruggiero, Sven Bergmann, Mika Kähönen, Jorma Viikari, Tiit Nikopensius, Michael Province, Shamika Ketkar, Helen Colhoun, Alex Doney, Antonietta Robino, Bernhard K Krämer, Laura Portas, Ian Ford, Brendan M Buckley, Martin Adam, Gian-Andri Thun, Bernhard Paulweber, Margot Haun, Cinzia Sala, Paul Mitchell, Marina Ciullo, Stuart K Kim, Peter Vollenweider, Olli Raitakari, Andres Metspalu, Colin Palmer, Paolo Gasparini, Mario Pirastu, J Wouter Jukema, Nicole M Probst-Hensch, Florian Kronenberg, Daniela Toniolo, Vilmundur Gudnason, Alan R Shuldiner, Josef Coresh, Reinhold Schmidt, Luigi Ferrucci, David S Siscovick, Cornelia M van Duijn, Ingrid B Borecki, Sharon L R Kardia, Yongmei Liu, Gary C Curhan, Igor Rudan, Ulf Gyllensten, James F Wilson, Andre Franke, Peter P Pramstaller, Rainer Rettig, Inga Prokopenko, Jacqueline Witteman, Caroline Hayward, Paul M Ridker, Afshin Parsa, Murielle Bochud, Iris M Heid, W H Linda Kao, Caroline S Fox, Anna Köttgen
In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations.

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Nov
2012

Allelic polymorphism of the apolipoprotein E (ApoE) gene (ApoE ε2, ApoE ε3 and ApoE ε4 alleles) gives rise to three protein isoforms (ApoE2, ApoE3 and ApoE4) that differ by 1 or 2 amino acids. Inheritance of the ApoE ε4 allele is a risk factor for developing Alzheimer's disease (AD). The potential diagnostic value of ApoE protein levels in biological fluids (i.

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Aug
2012

Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding.

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Dec
1969

Aggregates of the microtubule-associated protein Tau are neuropathological hallmark lesions in Alzheimer's disease (AD) and related primary tauopathies. In addition, Tau is genetically implicated in a number of human neurodegenerative disorders including frontotemporal dementia (FTD) and Parkinson's disease (PD). The exact mechanism by which Tau exerts its neurotoxicity is incompletely understood.

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Dec
1969

Late-life dementia results from non-modifiable risk factors such as age and genetics, modulated by deleterious and protective environmental factors among which nutrition may play a major role. This paper highlights five major recent contributions of the French Three-City (3C) and PAQUID epidemiological studies to Alzheimer's disease (AD) knowledge, targeting genetic and dietary risk factors, and the impact of cognitive decline in daily living. The 3C study contributed to a large genome-wide association study to identify new genetic risk factors for AD.

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Dec
1969

By applying an imputation strategy based on the 1000 Genomes project to two genome-wide association studies (GWAS), we detected a susceptibility locus for venous thrombosis on chromosome 11p11.2 that was missed by previous GWAS analyses that had been conducted on the same datasets. A comprehensive linkage disequilibrium and haplotype analysis of the whole locus where twelve SNPs exhibited association p-values lower than 2.

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